Regulatory T cells (Tregs) exert various suppressive mechanisms to dampen the host immune response which can help tumor cells to escape immune surveillance. However, the prognostic value of tumor-infiltrating Tregs (Ti-Tregs) is controversial. We described, tumor-associated tertiary lymphoid structures (TLS) in lung cancers, shown that they are critical for the local coordination and polarization of protective immunity and are able to imprint the behavior of intra-tumoral CD8+ T cells. The aim of the study was to determine the role of Ti-Tregs in the shaping of the local immune response in the context of TLS. We studied the differentiation, activation, immunosuppression, and immune checkpoint (ICP) status of Ti-Tregs in different areas of human lung tumors on a prospective cohort of 50 lung cancer specimens.
In lung cancer patients, CD3+FoxP3+ cells were detected in different zones of the tumor i.e. the tumor stroma (TLS and non-TLS areas) and to a lesser extend in tumor nests. They express CD4 and all markers of human Tregs. As observed for conventional CD4+ T cells, Ti-Tregs show central-memory and effector-memory phenotype. Based on the expression of activation, immunosuppression and ICP (gene and protein level), Tregs exhibit a fully activated phenotype in tumor compared to distant sites of NSCLC patients. Interestingly, Ti-Tregs display a common phenotype in TLS versus out TLS but with some key specificities regarding immune checkpoint expression.
In conclusion, the presence of several Ti-Treg subsets in lung tumor suggests they may use distinct mechanisms to exert their immunosuppressive functions in the different tumor areas.
Citation Format: Priyanka DEVI, Sylvain Leveugle, Jeremy Goc, Helene Kaplon, Claire Germain, Samantha Knockaert, Pierre Validire, Diane Damotte, Sandrine Katsahian, Wolf Herve Fridman, Catherine Sautes-Fridman, Myriam Lawand, Marie-Caroline Dieu-Nosjean. Identity card of tumor-infiltrating regulatory T cells in the context of tertiary lymphoid structures in lung cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-273.