Role of fibrosarcoma-induced CD11b+ myeloid cells and tumor necrosis factor-α in B cell responses

Oncogene. 2022 Mar;41(10):1434-1444. doi: 10.1038/s41388-022-02187-z. Epub 2022 Jan 15.

Abstract

The role of B cells in the anti-tumor immune response remains controversial. An increase in the number of B cells in the peripheral blood of some tumor patients has been associated with poor immunotherapy efficacy. However, the mechanism leading to the generation of these cells is not well-described. Using a fibrosarcoma model, we show that intraperitoneal administration of a xenogeneic antigen in tumor-bearing mice evokes large increases in antigen-specific serum immunoglobulin formation compared to tumor-naïve mice. An inability of tumor-bearing mice to induce enhanced antibody production after myeloid cell depletion suggests the antibody responses are CD11b+ myeloid cell-dependent. In vitro, CD11b+ myeloid cells promoted B cell proliferation, activation, and survival. High levels of tumor necrosis factor (TNF)-α were produced by CD11b+ cells, and TNF-α blockade inhibited B cell responses. CD11b+ cells appear to be important promoters of B cell responses and targeting B cells may increase the efficacy of immunotherapy in tumor-bearing hosts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen
  • Fibrosarcoma* / pathology
  • Humans
  • Immunotherapy
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / pathology
  • Tumor Necrosis Factor-alpha* / physiology

Substances

  • CD11b Antigen
  • Tumor Necrosis Factor-alpha