Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma
Abstract Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is responsive to immune checkpoint inhibitors (ICI). On rare occasion, MCC spontaneously regresses. It is speculated that this regression occurs when biopsy-induced antigen shedding precipitates an immune r...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00987-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849769730375680000 |
|---|---|
| author | Patrick Hallaert John W. Roman Mairead Baker Natasha T. Hill Jennifer L. Marte James L. Gulley Nicholas Logemann Courtney W. Hudgens Alexandre Reuben Isaac Brownell |
| author_facet | Patrick Hallaert John W. Roman Mairead Baker Natasha T. Hill Jennifer L. Marte James L. Gulley Nicholas Logemann Courtney W. Hudgens Alexandre Reuben Isaac Brownell |
| author_sort | Patrick Hallaert |
| collection | DOAJ |
| description | Abstract Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is responsive to immune checkpoint inhibitors (ICI). On rare occasion, MCC spontaneously regresses. It is speculated that this regression occurs when biopsy-induced antigen shedding precipitates an immune response. Here, we demonstrate the activation of an adaptive immune response in a patient whose tumor underwent spontaneous regression after biopsy. To evaluate the tumor immune microenvironment during regression, we performed quantitative immunohistochemical analysis and T-cell receptor (TCR) sequencing. Relative to baseline, the regressing tumor showed evidence of an activated cytotoxic T-cell response together with increased TCR clonality, greater representation of dominant T-cell clones, and the emergence of novel high-frequency T-cell clones. Similar changes in TCR profiles were observed in an MCC tumor undergoing ICI-induced regression. Taken together, our results provide evidence that the expansion of novel and pre-existing adaptive immune responses drives spontaneous MCC regression. |
| format | Article |
| id | doaj-art-66db3296771c4c5dab8a49dab63fb55c |
| institution | DOAJ |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-66db3296771c4c5dab8a49dab63fb55c2025-08-20T03:03:20ZengNature Portfolionpj Precision Oncology2397-768X2025-07-01911610.1038/s41698-025-00987-6Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinomaPatrick Hallaert0John W. Roman1Mairead Baker2Natasha T. Hill3Jennifer L. Marte4James L. Gulley5Nicholas Logemann6Courtney W. Hudgens7Alexandre Reuben8Isaac Brownell9Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH)Department of Dermatology, Naval Medical Center Portsmouth (NMCP)Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH)Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH)Center for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH)Center for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH)Department of Dermatology, Walter Reed National Military Medical Center (WRNMMC)Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer CenterDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH)Abstract Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is responsive to immune checkpoint inhibitors (ICI). On rare occasion, MCC spontaneously regresses. It is speculated that this regression occurs when biopsy-induced antigen shedding precipitates an immune response. Here, we demonstrate the activation of an adaptive immune response in a patient whose tumor underwent spontaneous regression after biopsy. To evaluate the tumor immune microenvironment during regression, we performed quantitative immunohistochemical analysis and T-cell receptor (TCR) sequencing. Relative to baseline, the regressing tumor showed evidence of an activated cytotoxic T-cell response together with increased TCR clonality, greater representation of dominant T-cell clones, and the emergence of novel high-frequency T-cell clones. Similar changes in TCR profiles were observed in an MCC tumor undergoing ICI-induced regression. Taken together, our results provide evidence that the expansion of novel and pre-existing adaptive immune responses drives spontaneous MCC regression.https://doi.org/10.1038/s41698-025-00987-6 |
| spellingShingle | Patrick Hallaert John W. Roman Mairead Baker Natasha T. Hill Jennifer L. Marte James L. Gulley Nicholas Logemann Courtney W. Hudgens Alexandre Reuben Isaac Brownell Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma npj Precision Oncology |
| title | Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma |
| title_full | Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma |
| title_fullStr | Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma |
| title_full_unstemmed | Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma |
| title_short | Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma |
| title_sort | spontaneous tumor regression and immunotherapy response demonstrate clonal t cell expansion in merkel cell carcinoma |
| url | https://doi.org/10.1038/s41698-025-00987-6 |
| work_keys_str_mv | AT patrickhallaert spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT johnwroman spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT maireadbaker spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT natashathill spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT jenniferlmarte spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT jameslgulley spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT nicholaslogemann spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT courtneywhudgens spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT alexandrereuben spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma AT isaacbrownell spontaneoustumorregressionandimmunotherapyresponsedemonstrateclonaltcellexpansioninmerkelcellcarcinoma |