P1.04-35 Identification and Characterization of a Unique KLRG1-Expressing Subset of CD4+FOXP3+ Tregs in Non-Small Cell Lung Cancer

Abstract

It is well established that CD4+FOXP3+ T regulatory cells (Tregs) contribute to dampening anti-tumor responses. Despite our improved understanding of their role in cancer, there remains a knowledge gap with respect to the clonal composition and heterogeneity of tumor-infiltrating Tregs in solid cancers. We addressed this outstanding issue by conducting comprehensive phenotypic profiling of Tregs present in lung adenocarcinomas of a genetically engineered mouse model of non-small cell lung cancer (NSCLC) as well as those in resected tumors of NSCLC patients. Multi-parameter flow cytometric analysis revealed that unlike the peripheral tissues, the tumor harbors a distinct sub-population of Tregs that express the co-inhibitory receptor, KLRG1. Compared to their negative counterparts, the KLRG1+ Treg subset exhibited heightened expression of a number of Treg signature proteins as well as higher levels of activation and memory molecular markers suggesting that they are a highly activated and differentiated Treg pool that is recruited to, or induced in the tumor microenvironment. Consistent with this phenotype, these KLRG1+ Tregs were superior in their capacity to suppress T cell proliferation relative to the KLRG1- cells. Collectively, these findings demonstrate that the tumor microenvironment in non-small cell lung cancer harbors a unique Treg sub-population that is characterized by dominant expression of KLRG1, and which represents a clonal pool with the most potent inhibition of T cell responses. These studies highlight the installment of distinct Treg subsets in NSCLC that have implications for regulation of anti-tumor responses.