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Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
Published on: May 6, 2019
Viral and tumor antigen-specific CD8 T-cell responses in Merkel cell carcinoma
Mahtab Samimi1, Houssem Benlalam2, Pascal Aumond2
1CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France; Laboratoire "Biologie des infections à polyomavirus", ISP1282 INRA Université de Tours, France; Dermatology Department, University of Tours, CHU Tours, Tours, France.
Abstract:
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer, which is immunogenic, regardless of the presence of MCPyV (80% of cases). The identification of MCC-specific epitopes recognized by CD8 T cells is crucial to expand the arsenal of immunotherapeutic treatments. Until now, most efforts focused on the identification of virus-specific epitopes, whereas immune responses directed against shared cellular tumor-specific antigens have not been evidenced. In this study, we measured T-cell responses against viral (n = 3) and tumor antigens (n = 47) from TILs derived from 21 MCC tumors. Virus-specific CD8 T-cell responses dominated MCC-specific immune responses, and we identified two new HLA-peptide complexes derived from the LT antigen, located in a region encompassing 3 previously identified epitopes. Finally, we show that MAGE-A3 antigen, frequently expressed by MCC tumors, was recognized by CD8 TILs from a virus-negative MCC tumor and thus could be a target for immunotherapy in this setting.
Insights
Merkel cell carcinoma (MCC) research identified new CD8 T-cell targets. Immune responses against tumor antigens, like MAGE-A3, offer potential for novel immunotherapy in virus-negative MCC cases.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with high immunogenicity.
- Immunotherapy for MCC is crucial, but requires identifying specific T-cell targets.
- Current research primarily focuses on virus-specific targets, neglecting tumor antigens.
Purpose of the Study:
- To investigate T-cell responses against viral and tumor antigens in MCC.
- To identify novel MCC-specific epitopes for immunotherapy development.
- To explore immune responses against shared cellular tumor antigens in MCC.
Main Methods:
- Analysis of T-cell responses from tumor-infiltrating lymphocytes (TILs) from 21 MCC tumors.
- Testing responses against 3 viral and 47 tumor antigens.
- Identification of HLA-peptide complexes and antigen recognition.
Main Results:
- Virus-specific CD8 T-cell responses were dominant in MCC.
- Two new HLA-peptide complexes from the LT antigen were identified.
- MAGE-A3 antigen was recognized by CD8 TILs in a virus-negative MCC tumor.
Conclusions:
- MCC harbors both virus-specific and tumor antigen-specific T-cell responses.
- LT antigen epitopes and MAGE-A3 represent potential targets for MCC immunotherapy.
- Targeting MAGE-A3 could benefit virus-negative MCC patients.
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