From gatekeepers to providers: regulation of immune functions by cancer-associated fibroblasts

Cancer-associated fibroblasts (CAFs) are major protumorigenic components of the tumor microenvironment in solid cancers. CAFs are heterogeneous, consisting of multiple subsets that display diverse functions. Recently, CAFs have emerged as major promoters of immune evasion. CAFs favor T cell exclusion and exhaustion, promote recruitment of myeloid-derived suppressor cells, and induce protumoral phenotypic shifts in macrophages and neutrophils. With the growing appreciation of CAF heterogeneity came the understanding that different CAF subpopulations may be driving distinct immune-regulatory effects, interacting with different cell types, and perhaps even driving opposing effects on malignancy. In this review we discuss the current understanding of CAF-immune interactions, their effect on tumor progression and therapeutic response, and the possibility of exploiting CAF-immune interactions as potential targets for cancer therapy.

Automated summary

Cancer-associated fibroblasts (CAFs) are heterogeneous and play a major role in promoting immune evasion in solid cancers. They contribute to T cell exclusion and exhaustion, recruit myeloid-derived suppressor cells, and induce pro-tumoral phenotypic changes in macrophages and neutrophils. The different subsets of CAFs have distinct immune-regulatory effects, interact with different cell types, and may have opposing effects on tumor malignancy.