Systemic and Local NK and Regulatory Cell Phenotypes and mTori-Induced Tumor-Specific Effector T-Cell Responses Are Key Players Favoring the Development of Squamous Cell Skin Carcinoma Among Kidney Transplant Patients
1Nephrology Laboratory, IDIBELL, Barcelona, Spain
2Nephrology Department and Renal Transplant Unit, Bellvitge University Hospital, Barcelona, Spain
3Kidney Transplant Unit, Germans Trias i Pujol University Hospital, Badalona, Spain.
Meeting: 2015 American Transplant Congress
Abstract number: C238
Keywords: Monitoring, Tumor recurrence
Session Information
Session Name: Poster Session C: Translational Biomarkers and Immune Monitoring
Session Type: Poster Session
Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Renal transplant patients are at higher risk of developing squamous cell carcinoma (SCC). Immunosuppressive agents promote an imbalance between effector and regulatory tumor-specific immune responses, favoring the development of malignancies. MTOR-inhibitors have been shown to reduce the incidence of cancer, as compared to CNI drugs.
Assessment of intratumoral and peripheral blood mononuclear cell immunophenotype as well as functional effector T-cell responses against SCC-related antigens (TSCR) was carried out in kidney transplant patients with SCC under CNI (KT-CNI-SCC) (n=42) or mTORi-based immunosuppressive regimens (KT-mTORi-SCC) (n=17). Immunophenotype and TSCR were re-assessed 12 months after conversion to mTORi in a group of 15 patients who developed SCC under CNI.
No-KT-SCC patients showed significantly higher intratumor cellular infiltrates than KT-SCC patients. Intratumoral Treg infiltrates were significantly higher among KT-mTORi-SCC patients than KT-CNI-SCCs (p<0.05). Tumor relapses within KT-CNI-SCC patients positively correlated with the number of circulating and tumor-infiltrating Tregs (p<0.05), whereas it negatively correlated with the number of NK cells both in the periphery and within tumor infiltrates (p<0.05). The number of tumor relapses in KT-mTORi-SCC positively correlated with the percentage of Tregs and CD56dim CD16+ NK-cells only circulating in peripheral blood. One-year after conversion to mTori, KT-CNI-SCC showed a significantly increase in Treg numbers in peripheral blood, reaching the same levels as No-KT-SCC (p<0.05).
Tumor-specific effector T-cell responses were significantly higher within No-KT-SCC than in KT-SCC population. 1-year after conversion, T-cell responses against MAGE-A1, MAGE-A3 and p53 SCC-related antigens were significantly increased (p<0.05), reaching similar levels than No-KT-SCC patients.
Development and progression of SCC after KT under CNI-based regimens seems to be directly influenced by an increased activity of Tregs but decreased presence of NK-cells, as well as to the suppression of TSCR responsive to mTor-inhibitors.
To cite this abstract in AMA style:
Crespo E, Lucia M, Fernandez L, Melilli E, Luque S, Lauzurica R, Cruzado J, Torras J, Grinyó J, Bestard O. Systemic and Local NK and Regulatory Cell Phenotypes and mTori-Induced Tumor-Specific Effector T-Cell Responses Are Key Players Favoring the Development of Squamous Cell Skin Carcinoma Among Kidney Transplant Patients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/systemic-and-local-nk-and-regulatory-cell-phenotypes-and-mtori-induced-tumor-specific-effector-t-cell-responses-are-key-players-favoring-the-development-of-squamous-cell-skin-carcinoma-among-kidney-tr/. Accessed October 10, 2024.« Back to 2015 American Transplant Congress