Activin A-Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer.

ABSTRACT:

Purpose

Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCC), although with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy.

Experimental design

Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naïve and resistant BCCs.

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 displ

SUBMITTER: Pich-Bavastro C 

PROVIDER: S-EPMC10472111 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature