Cover Image

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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Bauer, Kathrin (Author) , Nelius, Nina (Author) , Reuschenbach, Miriam (Author) , Koch, Moritz (Author) , Weitz, Jürgen (Author) , Steinert, Gunnar (Author) , Kopitz, Jürgen (Author) , Tariverdian, Mirjam (Author) , Knebel Doeberitz, Magnus von (Author) , Kloor, Matthias (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: Cancer immunology immunotherapy
Year: 2012, Volume: 62, Issue: 1, Pages: 27-37
ISSN:1432-0851
DOI:10.1007/s00262-012-1303-8
Online Access:Verlag, Volltext: http://dx.doi.org/10.1007/s00262-012-1303-8
Verlag, Volltext: https://doi.org/10.1007/s00262-012-1303-8
Get full text
Author Notes:Kathrin Bauer, Nina Nelius, Miriam Reuschenbach, Moritz Koch, Jürgen Weitz, Gunnar Steinert, Jürgen Kopitz, Philipp Beckhove, Mirjam Tariverdian, Magnus von Knebel Doeberitz, Matthias Kloor
Description
Summary: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.
Item Description:First online: 23 June 2012
Gesehen am 12.09.2018
Physical Description:Online Resource
ISSN:1432-0851
DOI:10.1007/s00262-012-1303-8

Similar Items