Abstract A185: Effective expansion of poly-functional tumor-reactive TILs from NSCLC correlates with an immune-engaged T-cell profile in tumor tissues

Non-small cell lung cancer (NSCLC) is the second most frequently occurring type of cancer. Because of the high mortality rates with the current treatment regimens, novel therapeutic approaches are warranted. The high mutational rate of the tumors, and the high level of T-cell infiltrates should render NSCLC patients eligible for autologous T-cell therapy. Here we show that tumor-infiltrating lymphocytes (TILs) from treatment naive, stage I-IIIa NSCLC tumors can be effectively expanded and reprogrammed. With an optimized detection essay for tumor-reactive T-cells, we observed that 13/17 tested TIL products (76.5%) from primary NSCLC tumor tissues contained cytokine-producing CD4+ and/or CD8+ T-cells in response to primary tumor digest. Tumor responses ranged from 0.5%-30%, and correlated well with activation markers on CD4+ and CD8+ T-cells. Importantly, 29.4% of the TIL products contained poly-functional T-cells that produced TNF-alfa and/or IL-2 in addition to IFN-gamma, and poly-functional T-cells correlated with high levels of tumor reactivity. Furthermore, high percentages of CD103+CD69+CD8+ T-cells, PD-1+CD4+ T-cells and FoxP3+CD25+CD4+ T-cells in the tumors were good predictors for the generation of highly tumor-reactive TIL products. In conclusion, we show that most NSCLCs contain tumor-specific T-cells that can be efficiently expanded and become highly poly-functional, depending on the initial T-cell profile of TILs. Our findings show the feasibility of culturing tumor-reactive TILs from NSCLC and provide keys to individualize adoptive T-cell therapy. Therefore, autologous T-cell therapy should be reconsidered as treatment for NSCLC patients. Citation Format: Rosa De Groot, Marleen M. van Loenen, Aurelie Guislain, Derk Amsen, John B.A.G. Haanen, Kim Monkhorst, Koen J. Hartemink, Monika C. Wolkers. Effective expansion of poly-functional tumor-reactive TILs from NSCLC correlates with an immune-engaged T-cell profile in tumor tissues [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A185.