Abstract
Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of bladder cancer (BLCA). Multiple studies have suggested that specific genetic mutations may serve as immune biomarkers for ICB therapy. Additionally, the nuclear receptor corepressor 1 (NCOR1) gene is a new player in the field of immune tolerance and the development of immune cells. In the ICI-treated-cohort, NCOR1 mutations may be used as a biomarker to predict the prognosis of BLCA patients receiving ICIs. The overall survival (OS) of the NCOR1-mutant (NCOR1-MT) group was significantly longer than that of NCOR1-wild-type (NCOR1-WT) group (P = 0·031; HR [95%CI]: 0·25 [0·12–0·52]). In the TCGA-BLCA-cohort, compared with NCOR1-WT, NCOR1-MT was associated with known predictors of ICB therapy efficacy, such as higher tumor mutational burden (TMB), neoantigen load and the number of mutations in the DNA damage-repair pathway. In addition, NCOR1-MT tumors had highly infiltrating TILs, activated antitumor immunity, and a high expression of immune-related genes, suggesting that NCOR1 mutations may serve as a potential biomarker to guide ICB therapy in BLCA.
Highlights
Bladder cancer is the ninth most common malignant tumor worldwide, with approximately 540,000 new cases and 180,000 deaths each year [1]
The results indicated that nuclear receptor corepressor 1 (NCOR1) mutations may be a potential biomarker for bladder cancer patients receiving immune checkpoint inhibitors (ICIs)
Survival analysis showed that the overall survival (OS) of NCOR1-MT patients after ICI treatment was significantly longer than that of NCOR1-WT patients (logrank test P = 0.031; hazard ratio (HR) = 0.25, 95% CI: 0.12−0.52); median OS (15 months versus not reached; Figure 1A)
Summary
Bladder cancer is the ninth most common malignant tumor worldwide, with approximately 540,000 new cases and 180,000 deaths each year [1]. Immune checkpoint blockade (ICB) therapies, especially anti-programmed cell death (ligand) 1 (anti-PD-(L)1) and anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), have provided new hope for bladder cancer patients. The United States Food and Drug Administration has approved five PD-(L) inhibitors for use as second-line or first-line treatment for advanced bladder cancer [3]. The overall response rates for immune checkpoint inhibitors (ICIs) are 13–24% [4,5,6], but most patients do not benefit from ICIs. screening biomarkers for immunotherapy is important to predict treatment response
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