免疫检查点抑制剂（ICIs）的出现改变了癌症治疗的前景。预测性生物标志物的估计有助于最大化ICIs治疗的效益。在这里，我们探讨了黑色素瘤中HYDIN突变（HYDIN-MUT）与ICIs疗效的关联。利用临床数据和已发表研究的测序数据评估了HYDIN-MUT和ICIs治疗在黑色素瘤患者中的关联。与其他肿瘤类型相比，HYDIN（36.14％）在黑色素瘤患者中具有最高的突变率。在抗PD-1治疗队列（n = 254）中，与HYDIN野生型（HYDIN-WT）患者相比，HYDIN-MUT患者在ICIs治疗后的生存期更长（HR = 0.590 [95％CI，0.410-0.847]，P = 0.004）；与HYDIN-WT患者比较，HYDIN-MUT患者的客观缓解率（ORR）和持久的临床益处（DCB）增加（ORR = 46.25，DCB = 56.00％）（ORR：P = 0.019；DCB：P = 0.060）。在抗CTLA4治疗队列（n = 174）中，HYDIN-MUT患者的生存期显著长于HYDIN-WT患者（HR = 0.549 [95％CI，0.366-0.823]，P = 0.003）；与HYDIN-WT患者相比，HYDIN-MUT患者的ORR和DCB比例显著较高（ORR 40.54％对14.42％，P = 0.031；DCB 45.76％对22.22％，P = 0.002）。进一步的基因集富集分析表明，在HYDIN-MUT患者中，DNA修复和抗肿瘤免疫显著增强。HYDIN突变是黑色素瘤患者ICIs疗效的潜在预测性生物标志物。

The advent of immune checkpoint inhibitors (ICIs) has altered the outlook for cancer treatment. The estimation of predictive biomarkers could contribute to maximizing the benefits from ICIs treatment. Here, we explored the association between HYDIN mutations (HYDIN-MUT) in melanoma and ICIs efficacy.Clinical data and sequencing data from published studies were utilized to assess the association between HYDIN-MUT and the efficacy of ICIs treatment in melanoma patients.Compared to other tumor types, HYDIN (36.14%) has the highest mutation rate in melanoma patients. In the anti-PD-1 treated cohort (n = 254), the HYDIN-MUT patients had a longer OS after ICIs treatment than the HYDIN wild-type (HYDIN-WT) patients (HR = 0.590 [95% CI, 0.410-0.847], P = 0.004); the objective response rate (ORR) and durable clinical benefit (DCB) were increased in patients with HYDIN-MUT (ORR = 46.25, DCB = 56.00%) compared to patients with HYDIN-WT (ORR = 30.99%, DCB = 42.76%) (ORR: P = 0.019; DCB: P = 0.060). In the anti-CTLA4 treated cohort (n = 174), HYDIN-MUT patients achieved significantly longer OS than HYDIN-WT patients (HR = 0.549 [95% CI, 0.366-0.823], P = 0.003); the proportion of ORR and DCB in HYDIN-MUT patients was significantly higher than that in HYDIN-WT patients (ORR 40.54% vs. 14.42%, P = 0.031; DCB 45.76% vs. 22.22%, P = 0.002). Further gene set enrichment analysis demonstrated that DNA repair and anti-tumor immunity were significantly enhanced in HYDIN-MUT patients.HYDIN mutations are a potential predictive biomarker of ICIs efficacy in melanoma patients.