Work

p57 increases immunotherapy efficacy by promoting cGAS-STING-mediated innate sensing in hepatocellular carcinoma

Year: 2025

Type: article

Abstract: Hyperactivation of the cell cycle in cancer cells suppresses antitumor immunity. The endogenous cyclin-dependent kinase inhibitor p57 is an important tumor suppressor and a potential therapeutic target for hepatocellular carcinoma (HCC). However, the immunomodulatory role of p57 remains unclear. Using samples from patients with HCC, we found that p57 expression correlated with an improved response to immune checkpoint inhibitors (ICIs) and increased CD8 + T cell infiltration. Mechanistically, p57 induced chromosomal instability and subsequently stimulated cGAS-STING-type I IFN signaling, leading to upregulation of the chemokines CCL5 and CXCL10, which promoted CD8 + T cell infiltration. Meanwhile, p57 also increased the expression of PD-L1 on the surface of HCC cells. Moreover, combining p57 overexpression with anti-PD-1 treatment synergistically inhibited tumor growth in vivo . Our studies demonstrated that p57 may serve as a biomarker for ICI efficacy, and increasing p57 expression is a potential therapeutic strategy to increase the efficacy of immunotherapy.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.116769