Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors.

While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction of patients are refractory to ICIs employed as standalone therapeutics, necessitating the development of combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest as combinatorial partners for ICIs, at least in part owing to their ability to initiate a tumor-targeting adaptive immune response. However, compared with either approach alone, combinatorial regimens involving ICD inducers and ICIs have not always shown superior clinical activity. Here, we discuss accumulating evidence on the therapeutic interactions between ICD inducers and immunotherapy with ICIs in oncological settings, identify key factors that may explain discrepancies between preclinical and clinical findings, and propose strategies that address existing challenges to increase the efficacy of these combinations in patients with cancer.
Competing Interests: Competing interests: LG holds research contracts with Lytix Biopharma, Promontory and Onxeo; Has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, AbbVie, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Imvax, Sotio, Promontory, Noxopharm, EduCom, and the Luke Heller TECPR2 Foundation; and holds Promontory stock options. The other authors have no conflicts of interest to declare.
(© 2024. The Author(s).)