Title: Antigen-presenting tumor B cells impact the phenotype of CD4 tumor infiltrating T cells in lung cancer patients
Abstract: Abstract The focus of immunotherapy has been on CD8 and CD4 tumor infiltrating lymphocytes (TILs), however, tumor infiltrating B cells (TIL-Bs) are understudied with no focus on their role as antigen presenting cells. We hypothesize that TIL-Bs help generate potent, long-term immune responses against cancer by presenting tumor antigens to CD4 TILs. Using un-manipulated, primary human B cells from fresh tumor, we generated a specific in vitro antigen presentation assay and observed three types of CD4 TIL responses when TIL-Bs presented autologous tumor antigens. There were activated responder CD4 TILs that proliferated when combined with TIL-Bs alone, which indicates stimulation with endogenous tumor antigens. There were antigen-associated responders that required autologous tumor lysate to elicit a CD4 TIL response, and there were patient CD4 TILs that did not respond to antigen presentation. Exhausted B cells have been described in chronic infection i.e. HIV, and thus, to parallel our studies to a model of chronic infection, we analyzed activated and exhausted TIL-Bs with our antigen presentation assay. If TIL-Bs were activated (HLADR+CD69+CD27+CD21+), the resultant CD4 TILs were T helper (anti-tumor) CD4 T cells and if the TIL-Bs were exhausted (HLADR+CD69+CD27−CD21−), the resultant CD4 TILs were T regulatory cells (pro-tumor). These data suggest that TIL-Bs influence CD4 TILs in NSCLC patient tumors. In conclusion, determining if TIL-Bs are activated or exhausted in NSCLC patients will determine the extent of their anti-tumor function in human cancer. Ultimately, results from this study will dictate how to target TIL-Bs in future immunotherapies.
Publication Year: 2017
Publication Date: 2017-05-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 1
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