Collaboration between tumor-specific CD4+ T cells and B cells in anti-cancer immunity
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.
|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.;|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/27121060|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13887|