Macrophages facilitate tumor cell PD-L1 expression via an IL-1β-centered loop to attenuate immune checkpoint blockade.

ABSTRACT: Tumor-associated macrophages (TAMs) play critical roles in reprogramming other immune cells and orchestrating antitumor immunity. However, the interplay between TAMs and tumor cells responsible for enhancing immune evasion remains insufficiently understood. Here, we revealed that interleukin (IL)-1β was among the most abundant cytokines within the in vitro tumor-macrophage coculture system, and enhanced IL-1β expression was associated with impaired cytotoxicity of CD8⁺ T cells in human ovarian cancer, indicating the possibility that IL-1β mediated immunosuppression during tumor-TAMs crosstalk. Mechanistically, we demonstrated that IL-1β significantly boosted programmed death-ligand 1 (PD-L1) expression in tumor cells via the activation of the nuclear factor-κb signaling cascade.

SUBMITTER: Xu C 

PROVIDER: S-EPMC10063777 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature