Effector Antitumor and Regulatory T Cell Responses Influence the Development of Nonmelanoma Skin Cancer in Kidney Transplant Patients. Issue 9 (September 2017)

• Record Type: Journal Article
• Authors: Crespo, Elena; Fernandez, Loreto; Lúcia, Marc; Melilli, Edoardo; Lauzurica, Ricardo; Penin, Rosa Maria; Quer, Ariadna; Luque, Sergio; Quero, Maria; Manonelles, Anna; Torras, Joan; Cruzado, Josep Maria; Cañas, Laura; Grinyó, Josep Maria; Bestard, Oriol
• Is Part Of: Transplantation. Volume 101:Issue 9(2017)
• Publication Date: 2017-09
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000001759
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : 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 calcineurin inhibitors (CNI) could contribute to SCC development, whereas conversion to mammalian target of rapamycin inhibitors (mTOR-i) could recover this protective immune response. Methods: Peripheral tumor-specific T cell responses against main SCC-derived antigens using the IFN-γ enzyme-linked immunospot assay and intratumor (IT) and circulating immune phenotypes (CD4 + T, CD8 + T, CD20 + B, CD56 + NK, FOXP3 + regulatory T [Treg] cells) 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 IT infiltrates and tumor-specific T cell responses than NoKT-SCC, and intratumoral and circulating FOXP3 + Treg cells were higher in KT-mTORi-SCC ( P < 0.05). Tumor-specific T cell responses were significantly lower in KT-CNI-SCC than KT-mTORi-SCC and NoKT-SCC and predicted SCC relapses (area under the curve = 0.837; P < 0.05). One-year after mTOR-i conversion, a significant increase in FOXP3 + Treg cell numbers and tumor-specific T cell responses were observed, reaching similar levels than KT-mTORi-SCC and NoKT-SCC patients. Conclusions: Tumor-specific T cell responses are strongly impaired in CNI-treated patients but recover after mTOR-i conversion, reducing SCC relapses. Abstract : In a cross-sectional study of 59 kidney transplant recipients with a squamous cell carcinoma (on CNI or mTOR inhibitor-based immunosuppression), the authors demonstrate weaker tumor-specific T cell responses in CNI-treated patients who recover after conversion to mTOR inhibitors. Supplemental digital content is available in the text.