Targeting the anti-tumor function of B cells in non-small cell lung cancer patient tumors (TUM9P.1008)

2015 
Understanding the function of tumor infiltrating lymphocytes (TILs) in NSCLC patient tumors will contribute to the development of rationally designed treatments and an increase in the current 18% survival rate. We hypothesize that TIL-Bs help generate potent, long-term immune responses against cancer. We used un-manipulated, primary human B cells from fresh tumor and tumor adjacent lung tissue to determine the phenotype and function of TIL-Bs in NSCLC patients. The total number of B cells at the site of the tumor versus the tumor-adjacent tissue was increased compared to other immune subsets. In analyzing the markers of activation and exhaustion, we observed a spectrum of activation of TIL-Bs. Further, we observed that TIL-Bs present autologous tumor antigens to CD4 TILs in a subset of NSCLC patients. These data suggest that some patients have functional TIL-Bs and some patients have nonfunctional TIL-Bs; TIL-Bs that could not present tumor-specific antigens had higher expression of B cell exhaustion markers. Lastly, we are combining blockade of the immune inhibitory PD-1:PD-L1 pathway in our antigen presentation assays because PD-1 expression is increased on CD4 TILs in our NSCLC patient tumors. Results from this study will advance the understanding of the anti-tumor function of TIL-Bs in solid tumors and will develop a model of B cell exhaustion in human cancer. Ultimately, we will predict which TIL-B functions to target in future NSCLC immunotherapies.
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