本研究旨在通过在电子数据库中进行系统文献检索（直至2021年5月31日）以确定与免疫检查点抑制剂（ICIs）疗效相关的基因组变异子类型。将包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和持久的临床利益（DCB）等主要结果与肿瘤基因组特征相关联。共纳入了14个研究中1546名肺癌患者的可用基因型数据。其中，有Kirsten大鼠肉瘤病毒致癌基因同源物G12C（KRASG12C）突变联合肿瘤蛋白P53（TP53）突变的患者出现了ICI治疗的良好疗效。此外EGFR经典激活突变（包括EGFRL858R和EGFR Δ19）的患者，在OS（校正危险比（HR）为1.40，95％置信区间（CI）为1.01‍‒‍1.95，P=0.0411）和PFS（校正HR为1.98，95％CI为1.49‍‒‍2.63，P<0.0001）方面表现出更糟糕的结果，而EGFRT790M的经典激活突变与未携带EGFRT790M的经典激活突变在OS（校正HR为0.96，95％CI为0.48‍‒‍1.94，P=0.9157）或PFS（校正HR为0.72，95％CI为0.39‍‒‍1.35，P=0.3050）方面无差异。值得注意的是，对于携带Usher综合征2A（USH2A）错义突变的患者，在OS（校正HR为0.52，95％CI为0.32‍‒‍0.82，P=0.0077）、PFS（校正HR为0.51，95％CI为0.38‍‒‍0.69，P<0.0001）、DCB（校正OR为4.74，95％CI为2.75‍‒‍8.17，P<0.0001）和ORR（校正OR为3.45，95％CI为1.88‍‒‍6.33，P<0.0001）方面表现出更好的结果。我们的发现表明，USH2A错义突变和KRASG12C与TP53突变联合起来与更好的疗效和生存结果有关，但EGFR经典突变无论是否与EGFRT790M结合起来，在ICIs疗法中的作用负面。我们的研究结果有助于为临床有效的免疫治疗选择精确的靶点。

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.