Spontaneous Tumor Regression and Immunotherapy Response Demonstrate Clonal T-Cell Expansion in Merkel Cell Carcinoma

Authors

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

Publication Date

7-1-2025

Journal

NPJ Precision Oncology

DOI

10.1038/s41698-025-00987-6

PMID

40594889

PMCID

PMC12218097

PubMedCentral® Posted Date

7-1-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Oncology, Skin cancer, Tumour immunology

Published Open-Access

yes

Recommended Citation

Hallaert, Patrick; Roman, John W; Baker, Mairead; et al., "Spontaneous Tumor Regression and Immunotherapy Response Demonstrate Clonal T-Cell Expansion in Merkel Cell Carcinoma" (2025). Faculty, Staff and Student Publications. 4961.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4961