excision repair cross-complementing (ERCC) 家族编码蛋白在DNA损伤修复和维持基因组稳定方面起至关重要的作用。然而，ERCC家族在肿瘤预后和免疫检查点抑制剂（ICI）疗法有效性方面的确切作用尚不确定。本研究旨在探讨ERCC突变与预后以及对ICI的响应之间的关系。我们观察到，在两个独立的全癌系列中，ERCC突变患者表现出增强的无进展生存期（PFS）和总生存期（OS）。此外，与野生型亚组相比，这个突变亚组显示出更高的肿瘤突变负荷（TMB）。值得注意的是，在接受ICI治疗的全癌患者中，ERCC突变与更好的总生存期相关（HR 0.54，95% CI 0.42-0.70；P < 0.001）（N = 1661）。这些发现在另一个队列中得到了验证，在ERCC突变亚组的患者中，显示出改善的临床结果（HR 0.56，95% CI 0.37-0.84；P = 0.03）和较高的响应率（51.9% vs. 26.8%）的表现。进一步分析揭示，ERCC突变患者显示出升高的肿瘤新抗原负荷（TNB）水平和免疫反应细胞的增加浸润。我们的研究表明，ERCC突变与增强的免疫原性和改善的ICI疗效相关，因此有可能作为ICI治疗的生物标志物。© 2023. Springer Nature Limited.

The proteins encoded by the excision repair cross-complementing (ERCC) family are pivotal in DNA damage repair and maintaining genome stability. However, the precise role of the ERCC family in tumor prognosis and the effectiveness of immune checkpoint inhibitors (ICI) therapy remain uncertain. This study aimed to explore the connection between ERCC mutations and prognosis as well as the response to ICI. We observed that patients with ERCC mutations exhibited enhanced progression-free survival (PFS) and overall survival (OS) in two independent pan-cancer cohorts. Furthermore, this mutant subgroup showed higher tumor mutation burden (TMB) compared to the wild-type subgroup. Notably, ERCC mutations were associated with better OS (HR 0.54, 95% CI 0.42-0.70; P < 0.001) in pan-cancer patients who underwent ICI therapy (N = 1661). These findings were validated in a separate cohort, where patients in the ERCC mutant subgroup demonstrated improved clinical outcomes (HR 0.56, 95% CI 0.37-0.84; P = 0.03) and higher response rates (51.9% vs. 26.8%) than the wild-type subgroup. Further analysis revealed that patients with ERCC mutations displayed elevated tumor neoantigen burden (TNB) levels and increased infiltration of immune-response cells. Our study suggests that ERCC mutations are linked to enhanced immunogenicity and improved ICI efficacy, thus potentially serving as a biomarker for ICI therapy.© 2023. Springer Nature Limited.