Gene Summary

Gene:ITGAX; integrin subunit alpha X
Aliases: CD11C, SLEB6
Summary:This gene encodes the integrin alpha X chain protein. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as inactivated-C3b (iC3b) receptor 4 (CR4). The alpha X beta 2 complex seems to overlap the properties of the alpha M beta 2 integrin in the adherence of neutrophils and monocytes to stimulated endothelium cells, and in the phagocytosis of complement coated particles. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:integrin alpha-X
Source:NCBIAccessed: 31 August, 2019


What does this gene/protein do?
Show (11)
Pathways:What pathways are this gene/protein implicaed in?
Show (2)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Genetic Predisposition
  • Carcinoma, Lobular
  • Missense Mutation
  • Adenocarcinoma of Lung
  • Young Adult
  • Breast Cancer
  • Cancer Gene Expression Regulation
  • Ribonuclease H
  • Single Nucleotide Polymorphism
  • Insulin Resistance
  • Skin Cancer
  • 1-Acylglycerophosphocholine O-Acyltransferase
  • Biomarkers, Tumor
  • Leukemic Gene Expression Regulation
  • Cluster Analysis
  • Chronic Lymphocytic Leukemia
  • Retinoic Acid
  • SLC2A3 protein, human
  • Granulosa Cells
  • Cardiovascular Diseases
  • Diabetes Mellitus
  • Hairy Cell Leukemia
  • LPCAT2 protein, human
  • Chromosome 1
  • Cell Proliferation
  • CD Antigens
  • Neoplastic Cell Transformation
  • Integrin alpha Chains
  • HOTAIR long untranslated RNA, human
  • Integrins
  • CD11c Antigen
  • Tandem Mass Spectrometry
  • Prostate Cancer
  • Chromosome 16
  • Tissue Array Analysis
  • Melanoma
  • Cell Cycle
  • Transcriptome
  • Structural Homology, Protein
  • Chemokines, CXC
  • Oligonucleotide Array Sequence Analysis
  • Protein Structure, Tertiary
  • Proteomics
  • Genome-Wide Association Study
Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (7)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: ITGAX (cancer-related)

Wang JQ, Tang Y, Li QS, et al.
PARG regulates the proliferation and differentiation of DCs and T cells via PARP/NF‑κB in tumour metastases of colon carcinoma.
Oncol Rep. 2019; 41(5):2657-2666 [PubMed] Free Access to Full Article Related Publications
The present study investigated the effect of poly(ADP‑ribose) glycohydrolase (PARG) on the immune response in tumour metastases of colon carcinoma. CT26 cells were transfected with lentivirus PARG‑short hairpin RNA (shRNA). A liver metastasis model of colon carcinoma was successfully established by splenic subcapsular inoculation of the various groups of CT26 cells into BALB/c mice. Next, changes in the liver metastases of colon carcinoma nodules and alterations in the survival times were observed in tumour‑bearing mice. The numbers of B220+DEC205+ dendritic cells (B220+DEC205+DC) and CD11c+CD11b+ dendritic cells (CD11c+CD11b+DC) in the spleen and liver were measured by the double‑label immunofluorescence assay. The distribution pattern of CD4+T cells and CD8+T cells in the spleen and liver was investigated by immunofluorescence staining. The expression levels of PARG, PARP and nuclear factor‑κB (NF‑κB) proteins in spleen transplant tumours and liver metastases of colon carcinoma were detected by western blotting. An ELISA was used to detect the levels of IL‑10 and TGF‑β in the serum of tumour‑bearing mice and from the supernatant of tumour cells. The numbers and grading of metastatic liver nodules in the PARG‑silenced group were clearly lower than those in the control group. The survival time of the PARG‑silenced group mice was longer than that in the control group. In the PARG‑silenced group, the levels of B220+DEC205+DC in the spleen and liver were lower and the numbers of CD11c+CD11b+DC in the spleen and liver were more than those in the control group. The ratio of CD4+/CD8+ in the spleen and liver in the PARG‑silenced group was increased compared with that in the control group (P<0.05). The levels of PARG, PARP and NF‑κB in spleen transplant tumours and liver metastases of colon carcinoma were lower in the PARG‑silenced group than in the control group. In addition, the levels of IL‑10 and TGF‑β in the serum of tumour‑bearing mice and supernatants of tumour cells were both reduced in the PARG‑silenced group compared with those in the control group. The present research suggests that the liver metastases of colon carcinoma could be restrained by silencing PARG. Likely, the silencing of PARG could suppress the expression of PARP and NF‑κB and subsequently suppress the secretion of IL‑10 and TGF‑α, finally affecting the proliferation and differentiation of DC and T cells.

Yahata T, Mizoguchi M, Kimura A, et al.
Programmed cell death ligand 1 disruption by clustered regularly interspaced short palindromic repeats/Cas9-genome editing promotes antitumor immunity and suppresses ovarian cancer progression.
Cancer Sci. 2019; 110(4):1279-1292 [PubMed] Free Access to Full Article Related Publications
Programmed cell death ligand 1 (PD-L1) on tumor cells suppresses anti-tumor immunity and has an unfavorable prognostic impact in ovarian cancer patients. We herein report the pathophysiological and therapeutic impacts of PD-L1 disruption in ovarian cancer. PD-L1 was genetically disrupted in the murine ovarian cancer cell line ID8 using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing. PD-L1 knockout (KO) and control ovarian cancer cells were intraperitoneally inoculated into syngeneic mice, and survival and tumor dissemination were evaluated. Survival times were significantly longer in the PD-L1-KO ID8-inoculated groups than in their control groups, and its therapeutic benefit was enhanced in combination with the cisplatin treatment. Tumor weights and ascites volumes were significantly lower in the PD-L1-KO ID8 groups than in their control groups. Immunohistochemical and immunofluorescence analyses showed that intratumoral CD4

Lee H, Lee HJ, Song IH, et al.
CD11c-Positive Dendritic Cells in Triple-negative Breast Cancer.
In Vivo. 2018 Nov-Dec; 32(6):1561-1569 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are prognostic markers in triple-negative breast cancer (TNBC). Our study analyzed the relationship between cluster of differentiation (CD)11c-positive dendritic cells (DCs) and TILs and TLSs to elucidate mechanisms of TIL influx.
MATERIALS AND METHODS: Immunohistochemical staining for CD4, CD8, and CD11c in tissue microarrays from 681 patients with TNBC was performed. The proportions of TILs and TLSs were reviewed. Two additional TNBC gene expression datasets were used.
RESULTS: CD11c expression showed a significantly positive correlation with the level of TILs and the number of CD4
CONCLUSION: We demonstrated a strong correlation of CD11c expression, which represents DCs, with TILs and TLSs in TNBC. Further investigation is warranted to identify therapeutic modalities that facilitate recruitment and activation of DCs.

Zhou Y, Liu F, Li C, et al.
Construction and Characterization of Adenovirus Vectors Encoding Aspartate-
J Immunol Res. 2018; 2018:9832467 [PubMed] Free Access to Full Article Related Publications
Dendritic cells (DCs) harboring tumor-associated antigen are supposed to be a potential immunotherapy for hepatocellular carcinoma (HCC). Aspartate-

Wehrhan F, Büttner-Herold M, Distel L, et al.
Galectin 3 expression in regional lymph nodes and lymph node metastases of oral squamous cell carcinomas.
BMC Cancer. 2018; 18(1):823 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Neck dissection is standard in surgical management of oral squamous cell carcinomas (oscc). However, the immunologic link between primary tumor and lymph nodes is insufficiently understood. Galectin 3 (Gal3) promotes M2 polarization of macrophages and contributes to immunosuppression. The current study analyzes the association between Gal3 expression in regional lymph nodes of oscc with histomorphologic parameters (T-, N-, L- Pn-stage, grading) of the primary tumor. Additionally, Gal3 expression is correlated with markers of macrophage polarization (M1 vs. M2).
METHODS: Preoperative diagnostic biopsies (n = 26), tumor resection specimens (n = 34), tumor-free lymph nodes (n = 28) and lymph node metastases (n = 10) of T1/T2 oscc patients were immunohistochemically analyzed for Gal3 and macrophage marker (CD68, CD11c, CD163 and MRC1) expression. The number of positive cells and the expression ratios were quantitatively assessed.
RESULTS: High Gal3 expression in tumor-free regional lymph nodes was significantly (p < 0.05) associated with increased tumor size. The epithelial compartment of lymph node metastases showed a significantly (p < 0.05) increased Gal3 expression compared to biopsies and tumor resection specimens. Cell density of M2 macrophages was significantly (p < 0.05) and positively correlated with the number of Gal3 expressing cells in lymph nodes and tumor specimens.
CONCLUSION: Gal3 expression in regional lymph nodes might be associated with oscc progression. The increased Gal3 expression in regional lymph nodes of larger tumors underlines the need of immunomodulatory treatment concepts in early-stage oscc. Blocking of Gal3 might be a therapeutic option in oral cancer.

Angelova EA, Medeiros LJ, Wang W, et al.
Clinicopathologic and molecular features in hairy cell leukemia-variant: single institutional experience.
Mod Pathol. 2018; 31(11):1717-1732 [PubMed] Related Publications
Hairy cell leukemia-variant is rare. Only a small number of cases have been reported in the literature with little cytogenetic or molecular data available. In this study, we describe the clinicopathologic and genetic features of 23 patients with hairy cell leukemia-variant (16 men and 7 women) with a median age of 70 years. Most patients had splenomegaly (90%), leukocytosis (77%), and lymphocytosis (82%); no patients had monocytopenia. Histologically, the bone marrow biopsy specimens showed a mixed pattern of predominantly interstitial and lesser intrasinusoidal infiltration by leukemic cells. In bone marrow aspirate smears most cells had villous cytoplasmic features and a small nucleolus. We describe unusual sites of hairy cell leukemia-variant involvement in 4 patients, including brain, omentum, terminal ileum, and skin at the time of initial presentation. Immunophenotyping showed monotypic B-cells positive for pan B-cell antigens, CD11c, and CD103, and negative for CD25 and annexin A1. Conventional cytogenetic or fluorescence in situ hybridization analysis showed deletions of 17p13/TP53 and 11q22/ATM gene in 5/12 (42%) and 2/9 (22%) cases, respectively. Sequencing of the variable region of IGVH showed mutations (>2% deviation from germline) in 40% of the cases assessed. MAP2K1 mutation (p.C121S) was seen in 1 of 14 (7%) patients tested. No BRAF V600E mutations were detected. The patients were treated in a heterogeneous manner, but most often with therapies designed for classical hairy cell leukemia and the 5-year overall survival was 84%. In summary, hairy cell leukemia-variant exhibits a heterogeneous spectrum of clinical, morphologic, immunophenotypic, and genetic features that may overlap with classic hairy cell leukemia and other hairy cell-like B-cell neoplasms. A subset of patients can have an aggressive clinical course. In our experience MAP2K1 mutations are uncommon in this disease.

Zheng J, Jia L, Mori S, Kodama T
Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes.
BMC Cancer. 2018; 18(1):608 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Surgical removal of primary tumors can promote the incidence of tumor metastasis. However, molecular mechanisms underlying this process remain unclear.
METHODS: We inoculated tumor cells expressing luciferase gene  into subiliac lymph node (SiLN) of the MXH10/Mo-lpr/lpr mice. The tumor-bearing SiLNs were surgically removed at a certain period of time after inoculation.
RESULTS: In vivo bioluminescence imaging system and histological staining revealed metastasis in lung, proper axillary lymph node (PALN) and liver. The lung metastasis rate in SiLN removal groups was significantly higher than in the control group using Fisher exact test. Mann-Whitney U-test indicated that the luciferase-positive tumor cells in the lung and liver were significantly higher than in the control groups. The lung samples in SiLN removal groups had strong expression of lysine oxidase (LOX). Moreover, the number of CD11b
CONCLUSIONS: Altogether, surgical removal of the tumor-bearing lymph node promoted tumor metastasis through changing the niche in lung and liver. Treatment targeting the metastatic niche might be an effective strategy to prevent tumor metastasis, thereby possibly increasing the survival and reducing the incidence of metastasis in cancer patients.

Hotblack A, Holler A, Piapi A, et al.
Tumor-Resident Dendritic Cells and Macrophages Modulate the Accumulation of TCR-Engineered T Cells in Melanoma.
Mol Ther. 2018; 26(6):1471-1481 [PubMed] Free Access to Full Article Related Publications
Ongoing clinical trials explore T cell receptor (TCR) gene therapy as a treatment option for cancer, but responses in solid tumors are hampered by the immunosuppressive microenvironment. The production of TCR gene-engineered T cells requires full T cell activation in vitro, and it is currently unknown whether in vivo interactions with conventional dendritic cells (cDCs) regulate the accumulation and function of engineered T cells in tumors. Using the B16 melanoma model and the inducible depletion of CD11c

Gulubova M, Aleksandrova E, Vlaykova T
Promoter polymorphisms in TGFB1 and IL10 genes influence tumor dendritic cells infiltration, development and prognosis of colorectal cancer.
J Gene Med. 2018; 20(2-3):e3005 [PubMed] Related Publications
BACKGROUND: Anti-inflammatory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β1 have a complex role in the development of colorectal cancer (CRC). Dendritic cells (DCs) are the cellular component of the inflammatory microenvironment in the tumor and infiltration of tumors by DCs is associated with better prognosis and fewer metastases.
METHODS: In the present study, we explored the role of two single nucleotide polymorphisms (SNPs) in the promoter regions of TGFB1 and IL10 genes and their associations with infiltrating DCs in CRC.A case-control study was designed. Genotyping was performed via the polymerase chain reaction-restriction fragment length polymorphism method and DC infiltration was determined immunohistochemically.
RESULTS: For the TGFΒ1 -509C/T SNP, we found that the T allele was less frequent in patients than in controls (p = 0.031) and the TT-genotype had a 2.74-fold lower risk for CRC than the CC-genotype (odds ratio = 0.365, 95% confidence interval = 0.15-0.88, p = 0.015). Additionally, the TT carriers had the shortest median survival (14.4 months) (p = 0.045). The C-allele genotypes had a significantly longer survival compared to TT carriers (p = 0.018). The CC genotype was associated with a lower cellular density of CD11c in the invasive margin of the tumor (p = 0.033), whereas there was an opposite finding for CD83+ DCs (p = 0.037). Carriers of A-allele genotypes of the IL10 -1080A/G SNP had significantly lower CD83+ cells (p = 0.046) in the tumor invasive margin.
CONCLUSIONS: The T-allele of the TGFB1 -509C/T SNP might be a protective factor for development of CRC, although, in the course of the disease, this variant allele might be associated with more unfavorable prognosis of the patients.

Ishibashi M, Yamaguchi H, Hirotani Y, et al.
Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers.
Arch Virol. 2018; 163(4):855-865 [PubMed] Related Publications
We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area. Parenchymal hepatocytes were negative for HLA-DQA1. HLA-DQA1-positive cells in the liver sinusoid were positive for CD68 (macrophages or Kupffer cells); those in the lymphocytic infiltrates were positive for CD20 (B cells) or CD3 (T cells). mRNA levels of antigen-presenting cell (APC) markers such as CD68 and CD11c were significantly upregulated in the HCV-high group and were correlated with HLA-DQA mRNA levels. CD8B mRNA (CD8

Troussard X, Cornet E
Hairy cell leukemia 2018: Update on diagnosis, risk-stratification, and treatment.
Am J Hematol. 2017; 92(12):1382-1390 [PubMed] Free Access to Full Article Related Publications
DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment.
DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation.
RISK STRATIFICATION: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. VH4-34 positive HCL cases are associated with poor prognosis RISK ADAPTED THERAPY: Purine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option.
MANAGEMENT OF PROGRESSIVE OR REFRACTORY DISEASE: It is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.

Bianco TM, Abdalla DR, Desidério CS, et al.
The influence of physical activity in the anti-tumor immune response in experimental breast tumor.
Immunol Lett. 2017; 190:148-158 [PubMed] Related Publications
This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analysed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow. Were used female Balb/c mice divided into 4 groups: two controls without tumor, sedentary (GI) and trained (GII) and two groups with tumor, sedentary (GIII) or trained (GIV). The physical activity (PA) was realized acoording swimming protocol. Tumor was induced by injection of 4T1 cells. All experiments were performed in biological triplicate. After the experimental period, the tumor was removed and the cells were identified by flow cytometry with labeling to CD4, CD8, CD11c, CD11b, CD80, CD86 and Ia, and intracelular staining IL-10, IL-12, TNF-α, IFN-γ, IL-17, Tbet, GATA3, RORγt and FoxP3. The bone marrow of the animals was obtained to analyse the derivated DCs by flow cytometry and culture cells to obtain the supernatant to measure the cytokines. Our results demonstrated that the PA inhibit the tumoral growth although not to change the number of TILS, but reduced expression of GATA-3, ROR-γT, related with poor prognosis, and TNF-α intracellular; however occur one significantly reduction in TIDCS, but these cells expressed more co-stimulatory and presentation molecules. Furthermore, we observed that the induced PA stimulated the gene expression of Tbet and the production of inflammatory cytokines suggesting an increase of Th1 systemic response. The results evaluating the systemic influence in DCs showed that the PA improve significantly the number of those cells in bone marrow as well the number of co-stimulatory molecules. Therefore, we could conclude that PA influence the innate immunity by interfering to promote in process of maturation of DCs both in tumor and systemically, that by its turn promote a modification in acquired immune cells, representing by T helper to induce an important alteration transcription factors that are responsible to maintain a suppressive microenviroment, and thereby, allowing the latter cells can thus activate antitumor immune response. The PA was able improve the Th1 systemic response by enhance to Tbet gene expression, promote a slightly increased of Th1-type cytokines and decrease Gata3 and Foxp3 gene expression in which can inhibit the Th1 immune response.

Kitamura H, Ohno Y, Toyoshima Y, et al.
Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy.
Cancer Sci. 2017; 108(10):1947-1952 [PubMed] Free Access to Full Article Related Publications
Overcoming the immunosuppressive state in tumor microenvironments is a critical issue for improving the efficacy of cancer immunotherapy. Interleukin (IL)-6, a pleiotropic cytokine, is highly produced in the tumor-bearing host. Previous studies have indicated that IL-6 suppresses the antigen presentation ability of dendritic cells (DC) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL-6/STAT3 signaling cascade on human DC and the subsequent induction of antitumor T cell immune responses. Tumor-infiltrating CD11b

Codreanu SG, Hoeksema MD, Slebos RJC, et al.
Identification of Proteomic Features To Distinguish Benign Pulmonary Nodules from Lung Adenocarcinoma.
J Proteome Res. 2017; 16(9):3266-3276 [PubMed] Free Access to Full Article Related Publications
We hypothesized that distinct protein expression features of benign and malignant pulmonary nodules may reveal novel candidate biomarkers for the early detection of lung cancer. We performed proteome profiling by liquid chromatography-tandem mass spectrometry to characterize 34 resected benign lung nodules, 24 untreated lung adenocarcinomas (ADCs), and biopsies of bronchial epithelium. Group comparisons identified 65 proteins that differentiate nodules from ADCs and normal bronchial epithelium and 66 proteins that differentiate ADCs from nodules and normal bronchial epithelium. We developed a multiplexed parallel reaction monitoring (PRM) assay to quantify a subset of 43 of these candidate biomarkers in an independent cohort of 20 benign nodules, 21 ADCs, and 20 normal bronchial biopsies. PRM analyses confirmed significant nodule-specific abundance of 10 proteins including ALOX5, ALOX5AP, CCL19, CILP1, COL5A2, ITGB2, ITGAX, PTPRE, S100A12, and SLC2A3 and significant ADC-specific abundance of CEACAM6, CRABP2, LAD1, PLOD2, and TMEM110-MUSTN1. Immunohistochemistry analyses for seven selected proteins performed on an independent set of tissue microarrays confirmed nodule-specific expression of ALOX5, ALOX5AP, ITGAX, and SLC2A3 and cancer-specific expression of CEACAM6. These studies illustrate the value of global and targeted proteomics in a systematic process to identify and qualify candidate biomarkers for noninvasive molecular diagnosis of lung cancer.

Umit EG, Baysal M, Durmus Y, Demir AM
CD11c expression in chronic lymphocytic leukemia revisited, related with complications and survival.
Int J Lab Hematol. 2017; 39(5):552-556 [PubMed] Related Publications
INTRODUCTION: Chronic lymphocytic leukemia (CLL) is a disorder of mature but dysfunctional monoclonal B cells. Microenvironment, antigenic stimulation and genetical mutations are demonstrated in etiopathogenesis. We aimed to evaluate the expression of CD11c in patients with CLL and its possible clinical significance.
METHODS: Data of 259 patients with CLL between 2010 and 2016 in Trakya University Faculty of Medicine, including age at diagnosis, sex, whole blood count, stage, percentage of CLL cells in bone marrow, line of treatments, development of Richter's transformation and secondary tumors, autoimmune complications, IgG level, prognostic cytogenetic analysis, and length of survival were recorded from files.
RESULTS: 151 patients were male (58.3%) and 108 were male (41.7%). Mean age was 70 (21-92) years. CD11c was observed to be positive (>%20) in 103 patients (39.8%). Development of Richter's transformation, secondary tumors and ITP was significantly frequent in patients with CD11c positivity (P values .000, .003, .000 respectively). Also, IgG levels were significantly lower in this group (P = .000). Hemoglobin level, RAI stage and bone marrow CLL infiltration percentage were statistically related with CD11c (P values .036, .037, .000 respectively). Finally, CD11c was statistically related (in positive group 70 months, negative group 79 months, P = .001).
CONCLUSION: CD11c, expressed not only in Hairy cell leukemia but also in dendritic cells, macrophages and monocytes is a differentiation marker for inflammation. Prolonged inflammation in the microenvironment of CLL cells may cause a susceptibility to autoimmune disorders and secondary tumors in CLL, in this way, an increase in mortality.

Uzonyi B, Mácsik-Valent B, Lukácsi S, et al.
Functional studies of chronic lymphocytic leukemia B cells expressing β
Immunol Lett. 2017; 189:73-81 [PubMed] Related Publications
The expression and role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in B cells are not yet explored in contrast to myeloid cells, where these β

Hu J, Zheng L, Shen X, et al.
MicroRNA-125b inhibits AML cells differentiation by directly targeting Fes.
Gene. 2017; 620:1-9 [PubMed] Related Publications
MicroRNA-125b (miR-125b) has been reported to be upregulated in several kinds of leukemia, suggesting that miR-125b plays a role in Leukemia development. In this study, it was shown that miR-125b expression level decreased in response to 1α, 25-dihydroxy-vitamin D3 (1,25D

Sanchez-Martin D, Uldrick TS, Kwak H, et al.
Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas.
J Natl Cancer Inst. 2017; 109(9) [PubMed] Free Access to Full Article Related Publications
Background: Primary effusion lymphoma (PEL) is a Kaposi's sarcoma herpes virus (KSHV)-induced lymphoma that typically arises in body cavities of HIV-infected patients. PEL cells are often co-infected with Epstein-Barr virus (EBV). "PEL-like" lymphoma is a KSHV-unrelated lymphoma that arises in body cavities of HIV-negative patients. "PEL-like" lymphoma is sometimes EBV positive. The derivation of PEL/"PEL-like" cells is unclear.
Methods: Mesothelial cells were cultured from body cavity effusions of 23 patients. Cell proliferation, cytokine secretion, marker phenotypes, KSHV/EBV infection, and clonality were evaluated by standard methods. Gene expression was measured by quantitative polymerase chain reaction and immunoblotting. A mouse model of PEL (3 mice/group) was used to evaluate tumorigenicity.
Results: We found that the mesothelia derived from six effusions of HIV-infected patients with PEL or other KSHV-associated diseases contained rare KSHV + or EBV + mesothelial cells. After extended culture (16-17 weeks), some mesothelial cells underwent a trans-differentiation process, generating lymphoid-type CD45 + /B220 + , CD5 + , CD27 + , CD43 + , CD11c + , and CD3 - cells resembling "B1-cells," most commonly found in mouse body cavities. These "B1-like" cells were short lived. However, long-term KSHV + EBV - and EBV + KSHV - clonal cell lines emerged from mesothelial cultures from two patients that were clonally distinct from the monoclonal or polyclonal B-cell populations found in the patients' original effusions.
Conclusions: Mesothelial-to-lymphoid transformation is a newly identified in vitro process that generates "B1-like" cells and is associated with the emergence of long-lived KSHV or EBV-infected cell lines in KSHV-infected patients. These results identify mesothelial cultures as a source of PEL cells and lymphoid cells in humans.

Ikeda Y, Kiyotani K, Yew PY, et al.
Clinical significance of T cell clonality and expression levels of immune-related genes in endometrial cancer.
Oncol Rep. 2017; 37(5):2603-2610 [PubMed] Free Access to Full Article Related Publications
Immune microenvironment characterized by T cell clonality as well as expression signatures of immune-related genes in endometrial cancer tissues may play significant roles in clinical outcome of patients. We aimed to investigate the clinical significance of immune-related gene expression and TCR repertoire in endometrial cancer. Using total RNAs extracted from 32 endometrioid endometrial cancer cases, we performed quantitative real-time PCR to measure mRNA expression levels of immune-related genes including TRB, CD8, GZMA, HLA-A, CD11c and PD-L1. Higher mRNA expression levels of CD8 (P=0.039) and CD11c (P=0.046) in the 32 tissue samples were significantly associated with longer progression-free survival (PFS). Expression levels of CD8 (P<0.001) and CD11c (P=0.048) were also significantly associated with longer PFS in 540 cases in TCGA database. We also performed T cell receptor β (TCRβ) sequencing of tumor-infiltrating lymphocytes (TILs) on an Illumina MiSeq platform. To evaluate clonal expansion of TCRβ clonotypes, we adjusted the number of abundant TCRβ clonotypes by TRB mRNA expression levels and examined TCR clonality with the expression levels of immune-related genes and clinicopathological factors. The cases with high clonal T cell expansion along with high PD-L1 expression in cancer tissues was related to higher mRNA expression levels of CD8 (P<0.001), GZMA (P<0.001) and HLA-A (P=0.027), showed a significantly longer PFS (P=0.015), indicating a possibility that these parameters may serve as faborable prognostic factors. Considering clinical stage, mRNA expression of CD8 (P=0.037), GZMA (P=0.027) and HLA-A (P=0.022) was significantly higher in tumors at an early stage. Thus, we identified clinical and prognostic significance of immune microenvironment including the T cell clonality of TILs as well as PD-L1 and CD11c mRNA expression levels in endometrial cancer tissues.

Dunoyer-Geindre S, Rivier-Cordey AS, Tsopra O, et al.
Effect of ATRA and ATO on the expression of tissue factor in NB4 acute promyelocytic leukemia cells and regulatory function of the inflammatory cytokines TNF and IL-1β.
Ann Hematol. 2017; 96(6):905-917 [PubMed] Free Access to Full Article Related Publications
The characteristic hemorrhages of acute promyelocytic leukemia (APL) are caused in part by the high expression of tissue factor (TF) on leukemic cells, which also produce TNF and IL-1β, proinflammatory cytokines known to increase TF in various cell types. Exposure of NB4 cells, an APL cell line, to all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) rapidly and strongly reduced TF mRNA. Both drugs also reduced TNF mRNA, but later, and moreover increased IL-1β mRNA. The effect on procoagulant activity of cells and microparticles, as measured with calibrated automated thrombography, was delayed and only partial at 24 h. TNF and IL-1β inhibition reduced TF mRNA and activity only partially. Inhibition of the inflammatory signaling intermediate p38 reduced TF mRNA by one third but increased TNF and IL-1β mRNA. NF-κB inhibition reduced, within 1 h, TF and TNF mRNA but did not change IL-1β mRNA, and rapidly and markedly reduced cell survival, with procoagulant properties still being present. In conclusion, although we provide evidence that TNF, IL-1β, and their signaling intermediates have a regulatory function on TF expression by NB4 APL cells, the effect of ATRA and ATO on TF can only partially be accounted for by their impact on these cytokines.

Chatterjee J, Dai W, Aziz NHA, et al.
Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer.
Clin Cancer Res. 2017; 23(13):3453-3460 [PubMed] Related Publications

Al Mussaed E, Osman H, Elyamany G
Simultaneous existence of acute myeloid leukemia and chronic lymphocytic leukemia: a case report.
BMC Cancer. 2016; 16(1):739 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The simultaneous Occurrence of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) has been rarely reported. Most of these cases have been occurring more frequently as a secondary event in patients receiving chemotherapeutic agents for CLL.
CASE PRESENTATION: We describe a case of a 77-year-old man who presented with fatigue, pallor and lower limb pain and weakness. Initial laboratory studies showed Hb 7.7 g/dl, WBC 279.6 × 10(9)/1, PLT 143× 10(9)/1. The peripheral blood (PB) smear examination showed circulating blast cells (20 %) cells and 50 % lymphocytes, with smudge cells. A bone marrow examination showed infiltration by two discrete abnormal cell populations, one represents the leukemic blast cells (60 %) and the other represents small mature lymphocytes (30 %). The immunologic phenotype of blasts was characterized by the co-expression of CD13, CD33, CD14, CD4, CD15, CD64, HLA-DR, CD11c. Lymphocytes were characterized by a typical CLL immunophenotype: CD19+, CD5+, CD23+, CD20+ (dim) and negative for FMC7, CD34, CD10 and TdT. Cytogenetic studies were negative for CLL and AML panels. PCR assays for AML specific genetic abnormalities were negative. Immunoglobulin gene analysis established the clonal nature of the B-cell expansion. A final diagnosis of concomitant CLL and AML(FAB: M5) was made.
CONCLUSION: We have reported a case in which there was simultaneous presentation of AML and CLL. Both forms of leukemia were well documented by morphology, cytometric analysis and molecular studies. Our findings support the idea that this rare concurrence of AML and untreated CLL may represent two separate disease processes.

Takeda Y, Azuma M, Matsumoto M, Seya T
Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific CD8(+) T cells during vaccine immunotherapy.
J Exp Clin Cancer Res. 2016; 35(1):143 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Dendritic cells (DCs) mount tumor-associated antigens (TAAs), and the double-stranded RNA adjuvant Poly(I:C) stimulates Toll-like receptor 3 (TLR3) signal in DC, which in turn induces type I interferon (IFN) and interleukin-12 (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation of CTLs correlates with tumor regression. How these potent cells expand with high quality is crucial to the outcome of CTL therapy. However, good markers reflecting the efficacy of DC-target immunotherapy have not been addressed.
METHODS: Using an EG7 (ovalbumin, OVA-positive) tumor-implant mouse model, we examined what is a good marker for active CTL induction in treatment with Poly(I:C)/OVA.
RESULTS: Simultaneous administration of Poly(I:C) and antigen (Ag) OVA significantly increased a minor population of CD8(+) T cells, that express CD11c in lymphoid and tumor sites. The numbers of the CD11c(+) CD8(+) T cells correlated with those of induced Ag-specific CD8(+) T cells and tumor regression. The CD11c(+) CD8(+) T cell moiety was characterized by its high killing activity and IFN-γ-producing ability, which represent an active phenotype of the effector CTLs. Not only a TLR3-specific (TICAM-1-dependent) signal but also TLR2 (MyD88) signal in DC triggered the expansion of CD11c(+) CD8(+) T cells in tumor-bearing mice. Notably, human CD11c(+) CD8(+) T cells also proliferated in peripheral blood mononuclear cells (PBMC) stimulated with cytomegalovirus (CMV) Ag.
CONCLUSIONS: CD11c expression in CD8(+) T cells reflects anti-tumor CTL activity and would be a marker for immunotherapeutic efficacy in mouse models and probably cancer patients as well.

Pigni M, Ashok D, Acha-Orbea H
Derivation and Utilization of Functional CD8(+) Dendritic Cell Lines.
Methods Mol Biol. 2016; 1423:39-49 [PubMed] Related Publications
It is notoriously difficult to obtain large quantities of non-activated dendritic cells ex vivo. For this reason, we produced and characterized a mouse model expressing the large T oncogene under the CD11c promoter (Mushi mice), in which CD8α(+) dendritic cells transform after 4 months. We derived a variety of stable cell lines from these primary lines. These cell lines reproducibly share with freshly isolated dendritic cells most surface markers, mRNA and protein expression, and all tested biological functions. Cell lines can be derived from various strains and knockout mice and can be easily transduced with lentiviruses. In this article, we describe the derivation, culture, and lentiviral transduction of these dendritic cell lines.

Jain D, Dorwal P, Gajendra S, et al.
CD5 positive hairy cell leukemia: A rare case report with brief review of literature.
Cytometry B Clin Cytom. 2016; 90(5):467-72 [PubMed] Related Publications
OBJECTIVE: The aberrant expression of CD5 in both HCL and HCL-v is a very rare event. Although a number of CD5 positive HCL and HCL-v cases have been reported, but these are far and few in between. We aimed to review the reported cases of CD5 positive HCL and its variant.
METHOD: We hereby report a case of CD5 positive HCL, with variations in PIK3CA and PDGFRA gene, along with a brief review of literature of the cases of CD5 positive HCL and its variant.
RESULTS AND CONCLUSION: The current case was positive for CD103, CD11c, CD25, and CD123 which has led the diagnosis to be of typical HCL. With the extensive literature review we found that only 26 cases of hairy cell leukemia [HCL and HCL-v] bearing CD5 expression have been reported so far. The positivity of CD5 is more common in HCL-v as compared to HCL. Additional prospective studies of CD5+ HCL and its variants are required to show whether they are a clinically significant subgroup of lymphoid malignancies. © 2016 International Clinical Cytometry Society.

Ohno Y, Kitamura H, Takahashi N, et al.
IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4(+) T cells.
Cancer Immunol Immunother. 2016; 65(2):193-204 [PubMed] Related Publications
Immunosuppression in tumor microenvironments critically affects the success of cancer immunotherapy. Here, we focused on the role of interleukin (IL)-6/signal transducer and activator of transcription (STAT3) signaling cascade in immune regulation by human dendritic cells (DCs). IL-6-conditioned monocyte-derived DCs (MoDCs) impaired the presenting ability of cancer-related antigens. Interferon (IFN)-γ production attenuated by CD4(+) T cells co-cultured with IL-6-conditioned MoDCs corresponded with decreased DC IL-12p70 production. Human leukocyte antigen (HLA)-DR and CD86 expression was significantly reduced in CD11b(+)CD11c(+) cells obtained from peripheral blood mononuclear cells (PBMCs) of healthy donors by IL-6 treatment and was STAT3 dependent. Arginase-1 (ARG1), lysosomal protease, cathepsin L (CTSL), and cyclooxygenase-2 (COX2) were involved in the reduction of surface HLA-DR expression. Gene expressions of ARG1, CTSL, COX2, and IL6 were higher in tumor-infiltrating CD11b(+)CD11c(+) cells compared with PBMCs isolated from colorectal cancer patients. Expression of surface HLA-DR and CD86 on CD11b(+)CD11c(+) cells was down-regulated, and T cell-stimulating ability was attenuated compared with PBMCs, suggesting that an immunosuppressive phenotype might be induced by IL-6, ARG1, CTSL, and COX2 in tumor sites of colorectal cancer patients. There was a relationship between HLA-DR expression levels in tumor tissues and the size of CD4(+) T and CD8(+) T cell compartments. Our findings indicate that IL-6 causes a dysfunction in human DCs that activates cancer antigen-specific Th cells, suggesting that blocking the IL-6/STAT3 signaling pathway might be a promising strategy to improve cancer immunotherapy.

Chevalier N, Mueller M, Mougiakakos D, et al.
Analysis of dendritic cell subpopulations in follicular lymphoma with respect to the tumor immune microenvironment.
Leuk Lymphoma. 2016; 57(9):2150-60 [PubMed] Related Publications
The immune cell composition of the follicular lymphoma (FL) tumor microenvironment is increasingly recognized as an important determinant for clinical outcome. Here, we explored frequency and distribution of dendritic cell (DC) subtypes in relation to regulatory T cells (Treg) by immunohistochemistry in lymph node biopsies from patients with de novo FL. We found that neoplastic follicles contained lower DC and higher Treg frequencies than hyperplastic follicles in control lymph nodes. Treg numbers particularly correlated with the subset of conventional CD11c(+ )DCs. Additionally, both a high intra- to interfollicular ratio of CD11c(+ )DCs and increased intrafollicular Treg frequencies were associated with decreased overall survival. This suggests that functional interactions between these cells may be relevant for FL progression/recurrence. The presence of CD11c(+ )DCs in the tumor microenvironment may assist tumor infiltration by Tregs, thus contributing to the suppression of an otherwise beneficial T-cell-dominated FL microenvironment.

Paiva B, Corchete LA, Vidriales MB, et al.
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Blood. 2016; 127(15):1896-906 [PubMed] Related Publications
Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) is associated with inferior survival in multiple myeloma (MM). Thus, characterization of the minor MRD subclone may represent a unique model to understand chemoresistance, but to our knowledge, the phenotypic and genetic features of the MRD subclone have never been investigated. Here, we compared the antigenic profile of MRD vs diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study and showed that the MRD subclone is enriched in cells overexpressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4), and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs diagnostic PCs was performed in 12 patients; 3 of them showed identical copy number alterations (CNAs), in another 3 cases, MRD clonal PCs displayed all genetic alterations detected at diagnosis plus additional CNAs that emerged at the MRD stage, whereas in the remaining 6 patients, there were CNAs present at diagnosis that were undetectable in MRD clonal PCs, but also a selected number of genetic alterations that became apparent only at the MRD stage. The MRD subclone showed significant downregulation of genes related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and may identify chemoresistant PCs in vitro. Altogether, our results suggest that therapy-induced clonal selection could be already present at the MRD stage, where chemoresistant PCs show a singular phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles. This trial was registered as #NCT01237249.

Rastogi P, Naseem S, Varma N, Varma S
Nucleophosmin mutation in de-novo acute myeloid leukemia.
Asia Pac J Clin Oncol. 2016; 12(1):77-85 [PubMed] Related Publications
OBJECTIVE: Acute myeloid leukemia (AML) with mutated nucleophosmin gene (NPM1) has distinctive clinical, hematological and molecular features, and is included as a provisional entity in 2008 World Health Organization classification. In this study, we analyzed the frequency and features of AML with mutated NPM1 in Indian patients.
METHODS: One-hundred consecutive patients of de-novo AML were evaluated for NPM1 mutation and their features were compared with unmutated NPM1 patients.
RESULTS: AML with mutated NPM1 was seen in 21% cases. There was female preponderance with median age of 51 years. Distinguishing Features in mutated group were less bleeding manifestations and bone pains; more lymphadenopathy; higher median total leukocyte and platelet count; less frequency of pancytopenia and more preserved megakaryocytes. Morphologically, cup-shaped nuclei in peripheral blood blasts correlated with NPM1 mutation (p <0.01), but not bone marrow blasts. Among the French-American-British subtypes, NPM1 mutation was seen in M1, M4 and M2 subtypes but not in M0 and M3. Immunophenotypically, there was statistically significant negativity for CD34, strong association with monocytic markers (especially CD11c), CD123 was seen at higher frequency and higher mean fluorescence intensity (MFI) values for CD33 were observed in mutated cases.
CONCLUSIONS: Important findings in this study that have not been highlighted in detail in previous studies in NPM1-mutated cases include less bleeding manifestations and bone pains, lower frequency of pancytopenia and more preserved magakaryocytes, higher CD123 expression and higher MFI values for CD33. Presence of blasts with cup-shaped nuclei correlated with NPM1 mutation.

Matutes E, Martínez-Trillos A, Campo E
Hairy cell leukaemia-variant: Disease features and treatment.
Best Pract Res Clin Haematol. 2015; 28(4):253-63 [PubMed] Related Publications
Hairy cell leukaemia-variant (HCL-V) is a rare B-cell malignancy that affects elderly males and manifests with splenomegaly, lymphocytosis and cytopenias without monocytopenia. The neoplastic cells have morphological features of prolymphocytes and hairy cells. The immunophenotype is that of a clonal B-cell CD11c and CD103 positive but, unlike classical HCL, CD25, CD123 and CD200 negative. The spleen histology is similar to classical HCL and the pattern of bone marrow infiltration is interstitial and/or intrasinusoidal. Mutations of the immunoglobulin heavy chain (IGVH) are seen in two thirds of cases with a preferential VH4-34 family usage. There is no distinct chromosomal abnormality but del17p13 and mutations of the TP53 gene are frequent. Mutations in the MAP2K1 gene have been documented in half of the cases. The course is chronic with median survivals of 7-9 years. Patients are refractory to purine analogues and the most effective therapy is the combination of 2-chlorodeoxyadenosine and Rituximab.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. ITGAX, Cancer Genetics Web: Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 31 August, 2019     Cancer Genetics Web, Established 1999