Development Of Exhaustion And Acquisition Of Regulatory Function By Infiltrating Cd8+Cd28-T Lymphocytes Dictate Clinical Outcome In Head And Neck Cancer

Simple SummaryCD8+ T lymphocytes are among the immune cells reputed to kill tumor cells. Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of infiltrating CD8+ T cells in a cohort of 30 HNSCC 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, we identified an intratumoral CD8+CD28- T cell subpopulation, which expressed markers of both exhausted (i.e., with impaired effector functions) and regulatory (i.e., exerting suppressive activities) cells. This suggests that in HNSCC effector T cells progressively undergo exhaustion and acquisition of regulatory properties, hampering their anti-tumor functions.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.