Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma.

ABSTRACT: The cytokine IL-18 has immunostimulatory effects but is negatively regulated by a secreted binding protein, IL-18BP, that limits IL-18's anticancer efficacy. A decoy-resistant form of IL-18 (DR-18) that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential has recently been developed. Here, we investigated the therapeutic potential of DR-18 in renal cell carcinoma (RCC). Using pantumor transcriptomic data, we found that clear cell RCC had among the highest expression of IL-18 receptor subunits and IL18BP of tumor types in the database. In samples from patients with RCC treated with immune checkpoint inhibitors, IL-18BP protein expression increased in the tumor microenvironment and in circulation within plasma in nonresponding patients, and it decreased in the ma

SUBMITTER: Schoenfeld DA 

PROVIDER: S-EPMC11721305 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature