Abstract 2948: A distinct CD8+tumor infiltrating lymphocyte subset is associated with high TIL density, enhanced cytotoxicity and improved survival in patients with lung cancer

High tumor infiltrating lymphocyte (TIL) density predicts for good prognosis in several cancers and therapies that boost the anti-tumor responses of cytotoxic lymphocytes (CTLs) have shown promise in the clinic. However, clinical responses to currently available immunotherapeutic agents vary considerably, the molecular basis of which is unclear. We performed global transcriptional profiling of CTLs in tumors and adjacent non-tumor tissue from 36 patients with early stage lung cancer to define the molecular features associated with robustness and heterogeneity of anti-tumor immune responses. We observed major differences in the transcriptional program of tumor-infiltrating CTLs (CD8+ TILs) that is shared across tumor subtypes. Pathway analysis revealed enrichment of genes in cell cycle, TCR activation and co-stimulation pathways, indicating tumor-driven expansion of presumed tumor antigen-specific CTLs. We also observed marked heterogeneity in the expression of molecules associated with TCR activation and immune checkpoints, and their expression was positively correlated with the density of tumor-infiltrating CTLs. Interestingly, TILhigh tumors were also enriched for a distinct CD8+ tumor infiltrating lymphocyte subset that appeared to have enhanced cytotoxicity and independently predicted improved survival in patients with lung cancer. In summary, we define the molecular fingerprint of tumor-infiltrating CTLs and identify a number of novel targets that may be important in modulating the magnitude and specificity of anti-tumor immune responses in lung cancer. Citation Format: Anusha Preethi Ganesan, Oliver Wood, Eva Garrido-Martin, Serena Chee, Toby Mellows, James Clarke, Daniela Samaniego-Castruita, Divya Singh, Gregory Seumois, Aiman Altezani, Edwin Woo, Peter Friedman, Gareth Thomas, Emma King, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H. Ottensmeier. A distinct CD8+ tumor infiltrating lymphocyte subset is associated with high TIL density, enhanced cytotoxicity and improved survival in patients with lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2948. doi:10.1158/1538-7445.AM2017-2948