Synthetic retinoid-mediated preconditioning of cancer-associated fibroblasts and macrophages improves cancer response to immune checkpoint blockade.

ABSTRACT:

Background

The proliferation of cancer-associated fibroblasts (CAFs) hampers drug delivery and anti-tumor immunity, inducing tumor resistance to immune checkpoint blockade (ICB) therapy. However, it has remained a challenge to develop therapeutics that specifically target or modulate CAFs.

Methods

We investigated the involvement of Meflin⁺ cancer-restraining CAFs (rCAFs) in ICB efficacy in patients with clear cell renal cell carcinoma (ccRCC) and urothelial carcinoma (UC). We examined the effects of Am80 (a synthetic retinoid) administration on CAF phenotype, the tumor immune microenvironment, and ICB efficacy in cancer mouse models.

Results

High infiltration of Meflin⁺ CAFs correlated with ICB efficacy in patients with ccRCC and UC. Meflin⁺

SUBMITTER: Owaki T 

PROVIDER: S-EPMC11263587 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature