Senescence and Immunotherapy: Redundant Immunomodulatory Pathways Promote Resistance

Abstract Senescent cancer cells alter their microenvironment through secretion of pro-inflammatory cytokines and chemokines called the senescence-associated secretory phenotype (SASP) and upregulation of immunoinhibitory proteins such as CD80 and programmed death-ligand 1. The senescence field is just beginning to explore the role of these changes on antitumor immunity and response to immunotherapy. In this Perspective, we highlight a new study that aimed to determine how senescent breast cancer cells are shielded from immunosurveillance via upregulation of redundant immunoinhibitory proteins in two distinct senescent populations. We also discuss recent articles regarding how the SASP alters the tumor immune microenvironment and response to immunotherapy. As many therapies used to treat cancers induce senescence, future work will need to better refine the composition of the SASP and heterogeneity of senescence in the tumor microenvironment to more completely understand how the immune compartment is regulated by senescent tumors.