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iNKT Cells Control Mouse Spontaneous Carcinoma Independently of Tumor-Specific Cytotoxic T Cells
Authors:Matteo Bellone  Monica Ceccon  Matteo Grioni  Elena Jachetti  Arianna Calcinotto  Anna Napolitano  Massimo Freschi  Giulia Casorati  Paolo Dellabona
Affiliation:1. Cellular Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, Istituto Scientifico San Raffaele, Milan, Italy.; 2. Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, Istituto Scientifico San Raffaele, Milan, Italy.; 3. Unità Operativa Anatomia Patologica, Istituto Scientifico San Raffaele, Milan, Italy.; 4. Università Vita Salute San Raffaele, Milan, Italy.;New York University, United States of America
Abstract:

Background

CD1d-restricted invariant NKT (iNKT) cells are a subset of T lymphocytes endowed with innate effector functions that aid in the establishment of adaptive T and B cell immune responses. iNKT cells have been shown to play a spontaneous protective role against experimental tumors. Yet, the interplay between iNKT and tumor-specific T cells in cancer immune surveillance/editing has never been addressed. The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a realistic model of spontaneous oncogenesis, in which the tumor-specific cytotoxic T cell (CTL) response undergoes full tolerance upon disease progression.

Principal Findings

We report here that lack of iNKT cells in TRAMP mice resulted in the appearance of more precocious and aggressive tumors that significantly reduced animal survival. TRAMP mice bearing or lacking iNKT cells responded similarly to a tumor-specific vaccination and developed tolerance to a tumor-associated antigen at comparable rate.

Conclusions

Hence, our data argue for a critical role of iNKT cells in the immune surveillance of carcinoma that is independent of tumor-specific CTL.
Keywords:
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