T cell responses against microsatellite instability-induced frameshift peptides and influence of regulatory T cells in colorectal cancer

• Verfasst von: Bauer, Kathrin [VerfasserIn]
• Verfasst von: Nelius, Nina [VerfasserIn]
• Verfasst von: Reuschenbach, Miriam [VerfasserIn]
• Verfasst von: Koch, Moritz [VerfasserIn]
• Verfasst von: Weitz, Jürgen [VerfasserIn]
• Verfasst von: Steinert, Gunnar [VerfasserIn]
• Verfasst von: Kopitz, Jürgen [VerfasserIn]
• Verfasst von: Tariverdian, Mirjam [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Verfasst von: Kloor, Matthias [VerfasserIn]
• Titel: T cell responses against microsatellite instability-induced frameshift peptides and influence of regulatory T cells in colorectal cancer
• Verf.angabe: Kathrin Bauer, Nina Nelius, Miriam Reuschenbach, Moritz Koch, Jürgen Weitz, Gunnar Steinert, Jürgen Kopitz, Philipp Beckhove, Mirjam Tariverdian, Magnus von Knebel Doeberitz, Matthias Kloor
• Jahr: 2013
• Jahr des Originals: 2012
• Umfang: 11 S.
• Fussnoten: First online: 23 June 2012 ; Gesehen am 12.09.2018
• Titel Quelle: Enthalten in: Cancer immunology immunotherapy
• Ort Quelle: Berlin : Springer, 1976
• Jahr Quelle: 2013
• Band/Heft Quelle: 62(2013), 1, Seite 27-37
• ISSN Quelle: 1432-0851
• DOI: doi:10.1007/s00262-012-1303-8
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Colorectal cancer
• Sach-SW: Frameshift peptides
• Sach-SW: High-level microsatellite instability
• Sach-SW: Immune response
• Sach-SW: Regulatory T cells
• K10plus-PPN: 1580891012

Abstract

High-level microsatellite-unstable (MSI-H) colorectal carcinomas (CRC) represent a distinct subtype of tumors commonly characterized by dense infiltration with cytotoxic T cells, most likely due to expression of MSI-H-related frameshift peptides (FSP). The contribution of FSP and classical antigens like MUC1 and CEA to the cellular immune response against MSI-H CRC had not been analyzed so far. We analyzed tumor-infiltrating and peripheral T cells from MSI-H (n = 4 and n = 14, respectively) and microsatellite-stable (MSS) tumor patients (n = 26 and n = 17) using interferon gamma ELISpot assays. Responses against 4 FSP antigens and peptides derived from MUC1 to CEA were compared with and without depletion of regulatory T cells, and the results were related to the presence of the respective antigens in tumor tissue. Preexisting FSP-specific T cell responses were detected in all (4 out of 4) tumor-infiltrating and in the majority (10 out of 14) of peripheral T cell samples from MSI-H CRC patients, but rarely observed in MSS CRC patients. Preexisting T cell responses in MSI-H CRC patients were significantly more frequently directed against FSP tested in the present study than against peptides derived from classical antigens MUC1 or CEA (p = 0.049). Depletion of regulatory T cells increased the frequency of effector T cell responses specific for MUC1/CEA-derived peptides and, to a lesser extent, T cell responses specific for FSP. Our data suggest that the analyzed FSP may represent an immunologically relevant pool of antigens capable of eliciting antitumoral effector T cell responses.