Spatially organized inflammatory myeloid-CD8⁺ T cell aggregates linked to Merkel-cell Polyomavirus driven Reorganization of the Tumor Microenvironment.

ABSTRACT: Merkel cell carcinoma (MCC) is an aggressive skin cancer with high propensity for metastasis, caused by Merkel-cell-polyomavirus (MCPyV), or chronic UV-light-exposure. How MCPyV spatially modulates immune responses within the tumor microenvironment and how such are linked to patient outcomes remains unknown. We interrogated the cellular and transcriptional landscapes of 60 MCC-patients using a combination of multiplex proteomics, in-situ RNA-hybridization, and spatially oriented transcriptomics. We identified a spatial co-enrichment of activated CD8⁺ T-cells and CXCL9⁺PD-L1⁺ macrophages at the invasive front of virus-positive MCC. This spatial immune response pattern was conserved in another virus-positive tumor, HPV⁺ head-and-neck cancer.

SUBMITTER: Haist M 

PROVIDER: S-EPMC12157451 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature