Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects

PLoS One. 2013 Oct 16;8(10):e76115. doi: 10.1371/journal.pone.0076115. eCollection 2013.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Antibodies / metabolism
  • Antigen-Antibody Complex / metabolism
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • CD11b Antigen / genetics
  • CD11b Antigen / metabolism
  • CD79 Antigens / genetics*
  • CD79 Antigens / metabolism
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Movement
  • Cell Proliferation
  • Chemokine CCL22 / metabolism
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Interleukin-6 / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Syk Kinase
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology


  • Adaptor Proteins, Signal Transducing
  • Antibodies
  • Antigen-Antibody Complex
  • B cell linker protein
  • CD11b Antigen
  • CD79 Antigens
  • Ccl22 protein, mouse
  • Cd79a protein, mouse
  • Chemokine CCL22
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse
  • Extracellular Signal-Regulated MAP Kinases