title: Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects.
abstract: The role of myeloid derived suppressor cells (MDSCs) in promoting tumorigenesis is well-established, and significant effort is being made to further characterize surface markers on MDSCs both for better diagnosis and as potential targets for therapy. Here we show that the B cell receptor adaptor molecule CD79a is unexpectedly expressed on immature bone marrow myeloid cells, and is upregulated on MDSCs generated in multiple different mouse models of metastatic but not non-metastatic cancer. CD79a on MDSCs is upregulated and activated in response to soluble factors secreted by tumor cells. Activation of CD79a on mouse MDSCs, by crosslinking with a specific antibody, maintained their immature phenotype (CD11b+Gr1+), enhanced their migration, increased their suppressive effect on T cell proliferation, and increased secretion of pro-tumorigenic cytokines such as IL-6 and CCL22. Furthermore, crosslinking CD79a on myeloid cells activated signaling through Syk, BLNK, ERK and STAT3 phosphorylation. In vivo, CD79+ myeloid cells showed enhanced ability to promote primary tumor growth and metastasis. Finally we demonstrate that CD79a is upregulated on circulating myeloid cells from lung cancer patients, and that CD79a+ myeloid cells infiltrate human breast tumors. We propose that CD79a plays a functional role in the tumor promoting effects of myeloid cells, and may represent a novel target for cancer therapy.
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Dror
authors.initials: D
authors.lastname: Luger
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Yang
authors.forename: Asaf
authors.initials: A
authors.lastname: Raviv
authors.forename: Douglas
authors.initials: D
authors.lastname: Weinberg
authors.forename: Subhadra
authors.initials: S
authors.lastname: Banerjee
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jane
authors.initials: J
authors.lastname: Trepel
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Lalage M
authors.initials: LM
authors.lastname: Wakefield
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D051925:CD79 Antigens / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D054422:Chemokine CCL22 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D000936:Antigen-Antibody Complex; C113939:B cell linker protein; D039481:CD11b Antigen; D051925:CD79 Antigens; C515483:Ccl22 protein, mouse; C497882:Cd79a protein, mouse; D054422:Chemokine CCL22; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases