EMBO J. 2025 Nov 28. doi: 10.1038/s44318-025-00650-7. Online ahead of print.
ABSTRACT
The successes of cancer immunotherapy have inspired research aiming to increase the number of immune-responsive cancers. The first effective immunotherapeutic strategies-immune checkpoint blockade (ICB) and CAR T cells-were designed to overcome limitations in CD8+ T cell recognition and killing of tumor cells. However, most solid tumors still do not respond to these measures and new treatment approaches are needed. Tumors evolve many strategies to avoid immune control. One way to identify immunotherapy strategies is to study what distinguishes immunotherapy-responsive and -unresponsive tumors. Another way is to identify the differences in tumors that emerge after carcinogen exposure in immunocompetent versus immunodeficient hosts. Still another way is to identify changes in gene expression in emerging tumors that enable them to escape immunosurveillance (known as tumor immunoediting). Evolving tumors suppress antigen processing and presentation to avoid triggering tumor-specific T cells but also repress key innate immune genes that transmit danger signals to immune cells. In this perspective, we discuss the roles of innate immunity in anti-tumor responses and consider how innate immunity could be harnessed to make tumors more immune-responsive.
PMID:41315764 | DOI:10.1038/s44318-025-00650-7
