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!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2397-768X |