Tumor-intrinsic ENO1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD-L1 immunotherapy in bladder cancer.

ABSTRACT: Immunotherapy has revolutionized cancer treatment, yet understanding immunotherapy resistance mechanisms remains challenging. Here, a CRISPR cas9 screening in vivo and an RNA-sequencing for clinical immunotherapy resistance BC samples identified enolase 1 (ENO1) as a potent regulator of anti-PD-L1 treatment efficacy. Investigation of clinical BC samples demonstrated a correlation between ENO1 overexpression and immune evasion in BC, evidenced by reduced CD8⁺ T cell infiltration and resistance to anti-PD-L1 therapy. Increased CD8⁺ T cell infiltration and function were indicative of antitumor immunity, which was elicited by ENO1 knockdown, which also suppressed carcinogenesis. Single-cell RNA sequencing demonstrated that wild-type (WT) and ENO1 knockout (KO) tumors have

SUBMITTER: Shen C 

PROVIDER: S-EPMC12261641 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature