Cancer Immunology, Immunotherapy

, Volume 62, Issue 1, pp 27–37 | Cite as

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

  • Kathrin Bauer
  • Nina Nelius
  • Miriam Reuschenbach
  • Moritz Koch
  • Jürgen Weitz
  • Gunnar Steinert
  • Jürgen Kopitz
  • Philipp Beckhove
  • Mirjam Tariverdian
  • Magnus von Knebel Doeberitz
  • Matthias Kloor
Original Article

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.

Keywords

Regulatory T cells Frameshift peptides High-level microsatellite instability Colorectal cancer Immune response 

Abbreviations

Bc

B lymphocytes

CRC

Colorectal carcinoma

FSP

Frameshift-derived peptides

IFN

Interferon

MSI-H

High-level microsatellite instability

MSS

Microsatellite stable

PBMC

Peripheral blood mononuclear cells

TIL

Tumor-infiltrating lymphocytes

Treg cells

Regulatory T cells

Supplementary material

262_2012_1303_MOESM1_ESM.pdf (9.5 mb)
Supplementary material 1 (PDF 9728 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Kathrin Bauer
    • 1
    • 2
  • Nina Nelius
    • 1
    • 2
  • Miriam Reuschenbach
    • 1
    • 2
  • Moritz Koch
    • 3
  • Jürgen Weitz
    • 3
  • Gunnar Steinert
    • 3
  • Jürgen Kopitz
    • 1
    • 2
  • Philipp Beckhove
    • 4
  • Mirjam Tariverdian
    • 3
  • Magnus von Knebel Doeberitz
    • 1
    • 2
  • Matthias Kloor
    • 1
    • 2
  1. 1.Department of Applied Tumor Biology, Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Cooperation Unit Applied Tumor BiologyDKFZ (German Cancer Research Center)HeidelbergGermany
  3. 3.Department of General, Visceral and Transplantation SurgeryUniversity Hospital HeidelbergHeidelbergGermany
  4. 4.Department of Translational ImmunologyGerman Cancer Research Center (DKFZ)HeidelbergGermany

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