Spatial biology reveals macrophage dysfunction in immunosuppressed non-melanoma skin cancer

This study employed single-cell multi-omic analyses to investigate the spatial distribution and transcriptional profiles of immune cells in NMSC from both immunocompetent (IC) and immunosuppressed (IS) patients.

Our results challenge the prevailing notion that immunosuppression is primarily driven by reduced immune cell abundance or lymphocytic dysfunction. We found that IS tumors retain all requisite immune cell populations but display functional suppression and disrupted spatial organization. Our data revealed a limited number of distinct programs, particularly in macrophages and their spatially organized niches, that are linked to restricted T-cell repertoire diversity and impaired clonal expansion, providing a mechanistic bridge between innate dysfunction and adaptive immune failure.