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Published on: October 30, 2013
CD8+ T-cell response against MUC1-derived peptides in gastrointestinal cancer survivors
Jasmin Dittmann1, Karin Keller-Matschke, Toni Weinschenk
1Department of Surgery, University Hospital, Tübingen, Germany.
Abstract:
The tumor-associated antigens CEA, MUC1 and Her2/neu are broadly expressed in gastrointestinal tumors, and are attractive candidates for targeting by T-cell-based immunotherapy. However, little is known about the natural cytotoxic T-cell response of patients suffering from colorectal or gastric carcinoma against these three as well as other antigens. Using a quantitative reverse transcription-polymerase chain reaction-based assay for IFN-gamma, we analyzed the CD8+ T-cell repertoire present in the blood of HLA-A2+ gastrointestinal tumor survivors against five known epitopes derived from CEA, MUC1 and Her2/neu. The results show that most of the patients (16 from 22 tested) have detectable, peripheral CD8+ T cells directed against at least one of these three proteins. Interestingly, the majority of these patients reacts to the two MUC1-derived HLA-A*0201 epitopes tested (14 from 16), demonstrating that this protein represents one dominant target for CD8+ T cells in gastrointestinal cancer.
Insights
Most gastrointestinal cancer patients have T-cells targeting tumor antigens like CEA, MUC1, and Her2/neu. MUC1 emerged as a dominant target for CD8+ T-cells in colorectal and gastric cancer patients.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumor-associated antigens such as CEA, MUC1, and Her2/neu are prevalent in gastrointestinal cancers.
- These antigens are potential targets for T-cell-based immunotherapies.
- The natural cytotoxic T-cell response against these antigens in gastrointestinal cancer patients is not well understood.
Purpose of the Study:
- To investigate the natural CD8+ T-cell response in patients with colorectal or gastric carcinoma against specific tumor-associated antigens.
- To identify dominant T-cell targets among CEA, MUC1, and Her2/neu in gastrointestinal cancer.
Main Methods:
- Analysis of the CD8+ T-cell repertoire in HLA-A2+ gastrointestinal tumor survivors.
- Utilized a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay to measure IFN-gamma production.
- Assessed T-cell responses against five known epitopes from CEA, MUC1, and Her2/neu.
Main Results:
- 16 out of 22 patients exhibited detectable peripheral CD8+ T cells targeting at least one of the studied antigens.
- A significant majority (14 out of 16) of responding patients showed reactivity to MUC1-derived epitopes.
- MUC1 was identified as a dominant target for CD8+ T cells in this patient cohort.
Conclusions:
- Gastrointestinal cancer patients possess a natural T-cell response against common tumor-associated antigens.
- MUC1 represents a primary target for CD8+ T-cell-mediated immunity in gastrointestinal malignancies.
- These findings support MUC1 as a promising target for T-cell-based immunotherapies in colorectal and gastric cancers.

