Analyses of tertiary lymphoid structures observed in cases of Merkel cell carcinoma showing spontaneous regression

AbstractMerkel cell carcinoma (MCC) is a high‐grade skin cancer, but spontaneous regression is observed at a markedly higher frequency than in other carcinomas. Although spontaneous regression is a phenomenon that greatly impacts treatment planning, we still cannot predict it. We previously reported on the prognostic impact of the presence or absence of tertiary lymphoid structures (TLS) and of Merkel cell polyomavirus (MCPyV) infection. To learn more about the spontaneous regression of MCC, detailed analyses were performed focusing on spontaneous regression cases. We collected 71 Japanese patients with MCC including 6 cases of spontaneous regression. Samples were analysed by immunostaining, spatial single‐cell analysis using PhenoCycler, and RNA sequencing using the next‐generation sequencer (NGS). All 6 cases of spontaneous regression were positive for MCPyV. TLS was positive in all 5 cases analysed. Spatial single‐cell analyses revealed that PD‐L1‐positive tumour cells were in close proximity to CD20‐positive B cell and CD3‐, 4‐positive T cells. Gene set enrichment analysis between MCPyV‐positive and TLS‐positive samples and other samples showed significantly high enrichment of “B‐cell–mediated immunity” gene sets in the MCPyV‐positive and TLS‐positive groups. In conclusion, TLS may play an important role in the spontaneous regression of MCC.