CAF-induced physical constraints controlling T cell state and localization in solid tumours

Abstract

Solid tumours comprise cancer cells that engage in continuous interactions with non-malignant cells and with acellular components, forming the tumour microenvironment (TME). The TME has crucial and diverse roles in tumour progression and metastasis, and substantial efforts have been dedicated into understanding the functions of different cell types within the TME. These efforts highlighted the importance of non-cell-autonomous signalling in cancer, mediating interactions between the cancer cells, the immune microenvironment and the non-immune stroma. Much of this non-cell-autonomous signalling is mediated through acellular components of the TME, known as the extracellular matrix (ECM), and controlled by the cells that secrete and remodel the ECM — the cancer-associated fibroblasts (CAFs). In this Review, we delve into the complex crosstalk among cancer cells, CAFs and immune cells, highlighting the effects of CAF-induced ECM remodelling on T cell functions and offering insights into the potential of targeting ECM components to improve cancer therapies. In this Review, Arpinati et al. summarize how the extracellular matrix, produced primarily by cancer-associated fibroblasts, impacts tumour progression, metastasis and therapy response through modulation of T cell-mediated antitumour immunity and propose routes to target these mechanisms therapeutically.