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

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.

Type Journal
ISBN 1949-2553 (Electronic) 1949-2553 (Linking)
Authors Guy, T. V.; Terry, A. M.; Bolton, H. A.; Hancock, D. G.; Zhu, E.; Brink, R.; McGuire, H. M.; Shklovskaya, E.; Fazekas de St. Groth, B.;
Publisher Name ONCOTARGET
Published Date 2016-01-01 00:00:00
Published Volume 7
Published Issue 21
Published Pages 30211-29
URL http://www.ncbi.nlm.nih.gov/pubmed/27121060
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?13887_13577/2016-Guy-Oncotarget.pdf