Tumor infiltrating B cells co-localize with CD4 T effector cells within organized tertiary lymphoid structures to present antigen and educate the anti-tumor immune response in human primary tumors

Abstract

Abstract Only 20% of cancer patients produce a durable response to current immunotherapies. Thus, a need exists to develop additional therapeutic strategies to treat these patients, which includes evaluation of other tumor infiltrating immune cells that could further augment the T cell response. Tumor infiltrating B cells (TIL-B) represent a possible target for immunotherapy due to their crucial role in the immune response. In fact, current data demonstrate that detection of TIL-Bs within tertiary lymphoid structures (TLS) correlate with increased survival in patients with solid tumors and enhanced response to anti-PD1 immunotherapy. We hypothesize that TIL-Bs help generate potent, long-term immune responses against cancer by presenting tumor antigens to CD4 TILs within TLS. We observed increased numbers of activated TIL-Bs in the primary tumors of head and neck squamous cell carcinoma and non-small cell lung cancer patients. We further assessed the transcriptional signature and location of TIL-Bs within the TME and demonstrated that they are adjacent to Th1 and Tfh CD4+ tumor infiltrating lymphocytes (TILs) within organized, germinal center containing TLS. Further, we generated an antigen presentation assay in vitro, and we observed increased CD4+ TIL responses when TIL-Bs presented autologous tumor antigens. These data suggest that TIL-Bs influence the function of CD4+ TILs in patient tumors within TLS. Ultimately, results from this study will increase effective targeting of TIL-Bs within patient primary tumors.