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

E. Crespo,¹ M. Lucia,¹ L. Fernandez,³ E. Melilli,² S. Luque,¹ R. Lauzurica,³ J. Cruzado,^1,2 J. Torras,^1,2 J. Grinyó,^1,2 O. Bestard.^1,2

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 November 21, 2024.

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