Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer
Daniela Fenoglio, Liliana Belgioia, Alessia Parodi, Francesco Missale, Almalina Bacigalupo, Alison Tarke, Fabiola Incandela, Simone Negrini, Stefania Vecchio, Tiziana Altosole, Sara Vlah, Giuseppina Astone, Francesca Costabile, Alessandro Ascoli, Francesca Ferrera, G. Schenone, Raffaele De Palma, Alessio Signori, Giorgio Peretti, Renzo Corvò, Gilberto Filaci
Abstract
Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28- T cells, and CD8+CD28-CD127-CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28- T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28-CD127-CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition.