Characterization of tumor-associated B-cell subsets in patients with colorectal cancer

Oncotarget. 2014 Jul 15;5(13):4651-64. doi: 10.18632/oncotarget.1701.

Abstract

Purpose: A precise understanding of the mechanisms by which human immune cell subsets affect tumor biology will be critical for successful treatment of cancer using immunotherapeutic approaches. Recent evidence suggests that B cells can both promote and inhibit the development and progression of tumors. The aim of this study was to characterize the composition of the B-cell infiltrates in colorectal cancers (CRC) in order to gain further insight into the role of B cells in CRC.

Experimental design: In this study we characterized B-cell subsets in primary tumors (n=38), metastases (n=6) and blood (n=46) of 51 patients with a diagnosis of CRC and blood of 10 healthy controls. B-cell subsets were analyzed by flow cytometry or immunohistochemistry.

Results: Peripheral blood of CRC patients contained a higher percentage of memory B cells than that of age-matched healthy controls. Furthermore, the percentage of B cells within tumors was higher than that in the peripheral blood of CRC patients while metastases were typically devoid of tumor-infiltrating B cells. Tumor-associated B cells were enriched for activated and terminally differentiated B cells. Relevant proportions of regulatory B cells could only be detected in advanced cancer and metastases.

Conclusion: B cells constitute a significant proportion of the immune infiltrate in CRC. The B-cell infiltrate of primary CRC is characterized by an accumulation of terminally differentiated memory B cells or plasma cells suggestive of a specific immune response against the tumor. However advanced tumors and metastases are also infiltrated by a considerable number of regulatory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Immunologic Memory / immunology
  • Immunophenotyping
  • Ki-67 Antigen / immunology
  • Ki-67 Antigen / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Plasma Cells / immunology
  • Plasma Cells / metabolism

Substances

  • Antigens, CD
  • Ki-67 Antigen