Conclusions
Altogether, our data identify the cellular and molecular plasticity of tumor microenvironment (TME) and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.
Purpose
Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCC), although with mitigated
Results
We identified subsets of intermingled cancer-associated fibroblasts (CAF) and macrophages contributing the most to CD8 T-cell exclusion and immunosuppression. Within this spatially resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A-mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T-cell exclusion. In independent datasets of human skin cancers, Activin A-conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI). Conclusions: Altogether, our data identify the cellular and molecular plasticity of tumor microenvironment (TME) and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.