Collaboration between tumor-specific CD4(+) T cells and B cells in anti-cancer immunity

Thomas V. Guy, Alexandra M. Terry, Holly A. Bolton, David G. Hancock, Erhua Zhu, Robert Brink, Helen M. McGuire, Elena Shklovskaya*, Barbara Fazekas De St Groth

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The role of B cells and antibodies in anti-tumor immunity is controversial, with both positive and negative effects reported in animal models and clinical studies. We developed a murine B16.F10 melanoma model to study the effects of collaboration between tumor-specific CD4+ T cells and B cells on tumor control. By incorporating T cell receptor transgenic T cells and B cell receptor isotype switching B cells, we were able to track the responses of tumor-reactive T and B cells and the development of anti-tumor antibodies in vivo. In the presence of tumor-specific B cells, the number of tumor-reactive CD4+ T cells was reduced in lymphoid tissues and the tumor itself, and this correlated with poor tumor control. B cells had little effect on the Th1 bias of the CD4+ T cell response, and the number of induced FoxP3+ regulatory cells (iTregs) generated from within the original naive CD4+ T cell inoculum was unrelated to the degree of B cell expansion. In response to CD4+ T cell help, B cells produced a range of isotype-switched anti-tumor antibodies, principally IgG1, IgG2a/c and IgG2b. In the absence of CD4+ T cells, B cells responded to agonistic anti-CD40 administration by switching to production of IgG2a/c and, to a lesser extent, IgG1, IgG3, IgA and IgE, which reduced the number of lung metastases after i.v. tumor inoculation but had no effect on the growth of subcutaneous tumors.

Original languageEnglish
Pages (from-to)30211-30229
Number of pages19
JournalOncotarget
Volume7
Issue number21
DOIs
Publication statusPublished - 24 May 2016
Externally publishedYes

Keywords

  • Antibody
  • B cell
  • CD4 T cell
  • Immune response
  • Immunity
  • Immunology and Microbiology Section
  • Melanoma

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