Spontaneous tumor regression and immunotherapy response demonstrate clonal T-cell expansion in Merkel cell carcinoma

Cancer research · Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is responsive to immune checkpoint inhibitors (ICI).

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.

The study demonstrates that spontaneous regression of MCC is accompanied by clonal T‑cell expansion and activation of cytotoxic T‑cell responses, linking innate immune dynamics to therapeutic outcomes and providing a rationale for exploring biomarker‑driven immunotherapy in a rare neuroendocrine skin cancer.

Evidence level: Számítógépes vagy elméleti. Modellből vagy adatbányászatból származó jel.

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