Cancer-Associated Fibroblasts in Inflammation and Antitumor Immunity

Tumor-associated inflammation (TAI) is a feature of essen-tially all cancers and can confer both tumor-promoting and-suppressive functions. Cancer-associated fibroblasts (CAF) comprise one very heterogeneous cellular component of the tumor microenvironment characterized by a high degree of plasticity. Recent single-cell sequencing analyses revealed dis-tinct CAF populations in various human cancers and helped to define key CAF subtypes, such as myofibroblastic, inflammatory, and antigen-presenting CAFs, with the first two being present in virtually all tumors. Importantly, these three CAF populations are involved in and modulate the positive and negative con-sequences of TAI. The remarkable plasticity of CAFs allows them to shift phenotypically and functionally in response to environ-mental changes. In this review, we describe how CAFs nurture tumor-promoting inflammation and suppress adaptive immu-nity. We also summarize the recently emerging evidence per-taining to tumor-suppressive CAF functions in the context of TAI. Finally, we summarize therapeutic concepts that aim at modulating CAF functions or depleting immunosuppressive CAFs to synergize with immunotherapy.

Automated summary

Tumor-associated inflammation (TAI) is a common feature in cancers, and cancer-associated fibroblasts (CAF) play a crucial role in modulating TAI. CAFs exhibit remarkable plasticity and can shift their phenotypes and functions in response to environmental changes. This review explores how CAFs contribute to tumor-promoting inflammation and suppress adaptive immunity, as well as the potential therapeutic strategies targeting CAFs in combination with immunotherapy.