Targeting senescent EGR1⁺ B cells enhances immunotherapy efficacy in esophageal squamous cell carcinoma.

ABSTRACT: The mechanisms for failure of neoadjuvant immune checkpoint blockade (NICB), an established therapy for patients with esophageal squamous cell carcinoma (ESCC), remain unclear. We integrated single-cell RNA data from patients with ESCC pre- and post-NICB, identifying a subset of senescent EGR1-expressing B cells that correlate with poor pathological responses. EGR1 was a key transcription factor regulating B cell senescence. EGR1⁺ B cells emerged as predictors of adverse outcomes in multiple cohorts. These senescent B cells, through senescence-associated secretory phenotype (SASP), drive chronic inflammation in the tumor microenvironment (TME), promoting the inducement of immunosuppressive TREM2⁺ tumor-associated macrophages (TAMs), thereby suppressing anti-tumor immu

SUBMITTER: Zhou P 

PROVIDER: S-EPMC12866087 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature