Effector Antitumor and Regulatory T Cell Responses Influence the Development of Nonmelanoma Skin Cancer in Kidney Transplant Patients.

Background: Chronic immunosuppression promotes Nonmelanocytic Squamous Cell Carcinoma (SCC) after kidney transplantation. Adaptive and innate immunity play a key role controlling tumor growth and are influenced by different immunosuppressive agents. We hypothesized that functional impairment of tumor-specific T cell responses due to CNI could contribute to SCC development, whereas conversion to mTOR-i could recover this protective immune response. Methods: Peripheral tumor-specific T cell responses against main SCC-derived antigens using the IFN-[gamma] ELISPOT assay and intratumor and circulating immune phenotypes (CD4+T, CD8+T, CD20+B, CD56+NK, FOXP3+Tregs) were explored in a cross-sectional analysis in 59 kidney transplant patients with SCC on CNI (KT-CNI-SCC) or mTOR-i (KT-mTORi-SCC), 25 nontransplants developing SCC (NoKT-SCC) and 6 healthy controls. Moreover, 25 KT-CNI-SCC were switched to mTOR-i and evaluated after 12 months. Results: Kidney transplant patients showed lower intratumor infiltrates and tumor-specific T cell responses than NoKT-SCC, and intratumoral and circulating FOXP3+Treg were higher in KT-mTORi-SCC (p

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