Double positive (DP) CD4+CD8+T cells with an exhausted phenotype in renal cell carcinoma (RCC) patients

Checkpoint inhibitors target the inhibitory receptors expressed by tumor infiltrating T cells in order to reinvigorate an anti-tumor immune response. Therefore, understanding T cell composition and phenotype in human tumors is crucial. We analyzed by flow cytometry tumor infiltrating lymphocytes from two independent cohorts of patients with different cancer types, including RCC, lung and colon cancer. T cells are usually either CD4+ or CD8+ with a small percentage of CD4+ CD8+ DP cells ( 5%, reaching 30-50% of T cells in some patients). These DP T cells express high level of PD1 and TIM-3 that tend to correlate with higher expression of PD1 and TIM-3 in conventional CD8 T cells. DP T cells also express markers of antigen-experienced T cells such as CD38 and HLA-DR. These results suggest that double positive T cells might be exhausted tumor specific T cells with the potential to be reactivated by checkpoint inhibitors. Citation Format: Laurence Menard, Paul Fischer, Bijal Kakrecha, Deborah Lee, Becky Penhallow, Nataly Manjarrez Orduno, Steven Nadler. Double positive (DP) CD4+CD8+ T cells with an exhausted phenotype in renal cell carcinoma (RCC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4687.