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目的:探讨F框/WD-40域蛋白7（FBXW7）基因突变对非小细胞肺癌（NSCLC）患者免疫治疗预后的影响。方法:（1）选取2019年1月至2021年6月南京医科大学第一附属医院肿瘤科接受免疫检查点抑制剂治疗的晚期NSCLC患者125例，男70例，女55例，年龄［n M（n Q1，n Q3）］为64（57，70）岁；收集其临床治疗及预后资料，分析FBXW7突变与免疫治疗疗效及预后的关系。（2）在cBioPortal数据库检索与免疫治疗相关的NSCLC数据集，共261例患者纳入研究，作为免疫治疗队列，男120例，女141例，年龄66（57，73）岁；其临床数据及基因突变数据均从cBioPortal数据库下载，分析FBXW7突变与NSCLC患者临床特征和免疫治疗预后的关系。（3）在癌症基因组图谱（TCGA）数据库下载1 030例NSCLC患者转录组和基因突变数据进行后续分析，作为TCGA队列，男633例，女397例，年龄为67（60，73）岁；分析FBXW7突变对免疫治疗疗效的影响，以及其影响NSCLC免疫治疗疗效的关键分子及其生物学功能。n 结果:125例NSCLC患者中，FBXW7突变率为5.6%（7/125）；7例患者的FBXW7突变类型均为截断突变，在接受免疫治疗后，部分缓解4例，疾病稳定2例，疾病进展 1例，客观缓解率（ORR）为4/7，疾病控制率（DCR）为6/7。FBXW7突变患者中位无进展生存期（PFS）为13.0个月（95%n CI：7.0~22.0个月），优于FBXW7野生型患者的4.0个月（95%n CI：2.0~11.5个月）（n P=0.046）。生物信息学分析显示，FBXW7突变型患者接受免疫治疗后临床获益更高。免疫治疗队列中FBXW7突变型患者的肿瘤突变负荷［n M（n Q1，n Q3）］为17.8（11.5，29.3）个/Mb，高于FBXW7野生型患者［5.7（3.0，10.4）个/Mb，n P=0.001］。TCGA队列中，FBXW7突变型患者的肿瘤突变负荷为15.9（4.2，28.1）个/Mb，基因插入或缺失来源的肿瘤新抗原为192.5（70.8，535.0）个，单核苷酸突变来源的肿瘤新抗原为363.0（194.8，534.8）个，均高于FBXW7野生型患者的5.6（3.2，8.9）个/Mb、53.0（12.0，131.0）个、83.5（34.0，178.0）个（n P=0.002、0.008、n P<0.001），表明FBXW7突变型肿瘤具有更强的免疫原性，可能产生强大的抗肿瘤免疫。FBXW7突变与T淋巴细胞的激活有关，表现为T淋巴细胞受体复合物与信号传导的激活。进一步对肿瘤免疫细胞浸润程度分析发现，FBXW7突变型肿瘤的CD8n +T淋巴细胞和M1型巨噬细胞浸润率分别为10%（8%，14%）、8%（4%，11%），均高于FBXW7野生型肿瘤的7%（4%，12%）、4%（1%，8%）（n P=0.049、0.046）。n 结论:FBXW7突变型NSCLC患者接受免疫治疗后临床获益更高，FBXW7基因突变具有作为NSCLC患者免疫治疗疗效预测标志物的可能性。“,”Objective:To explore the effect of F-box and WD-40 domain protein 7 (FBXW7) gene mutation on the prognosis of immunotherapy in patients with non-small cell lung cancer (NSCLC).Methods:(1) The clinical data of 125 patients with advanced NSCLC in the First Affiliated Hospital of Nanjing Medical University from January 2019 to June 2021 were collected. There were 70 males and 55 females, with a median age [n M (n Q1, n Q3)] of 64(57, 70) years. The correlation of FBXW7 mutation with immunotherapy efficacy and prognosis was analyzed. (2) The Data set of NSCLC patients treated with immunotherapy from cBioPortal database was downloaded. A total of 261 patients were included as immunotherapy group. There were 120 males and 141 females, with a median age of 66(57, 73) years. The association of FBXW7 mutation with clinical characteristics and prognosis of NSCLC patients was investigated. (3) The data of patients with NSCLC from the cancer genome atlas (TCGA) database were downloaded. A total of 1 030 patients were included as TCGA group. There were 633 males and 397 females, with a median age of 67(60, 73) years. The effect of FBXW7 mutation on the efficacy of immunotherapy was analyzed. The key molecules and their biological functions were also determinedn Results:Among the 125 NSCLC patients, the FBXW7 mutation rate was 5.6% (7/125). All FBXW7 mutation types was truncating mutation. In these FBXW7 mutation patients who received immunotherapy, 4 had partial response, 2 had stable disease, and 1 had progressive disease. The objective response rate (ORR) and disease control rate (DCR) were 4/7 and 6/7, respectively. The median progression-free survival (PFS) was 13.0 months (95%n CI: 7.0-22.0 months) for patients with FBXW7 mutation and 4.0 months (95%n CI: 2.0-11.5 months) for patients with FBXW7 wild type, with a statistically significant difference (n P=0.046). The bioinformatics analysis indicated that patients with FBXW7 mutation have higher clinical benefits from immunotherapy. Moreover, patients with FBXW7 mutation in immunotherapy group had higher tumor mutational burden (TMB) [n M (n Q1, n Q3): 17.8 (11.5, 29.3)/Mb] than those with FBXW7 wild type [5.7 (3.0, 10.4)/Mb, n P=0.001]. The TMB of patients with FBXW7 mutation in TCGA group was 15.9 (4.2, 28.1)/Mb, insertion-deletion (Indel) neoantigen was 192.5 (70.8, 535.0) and single nucleotide variant (SNV) neoantigen was 363.0 (194.8, 534.8), which were significantly higher than those of patients with FBXW7 wild type [5.6 (3.2, 8.9)/Mb, 53.0 (12.0, 131.0), 83.5 (34.0, 178.0), respectively] (n P=0.002, n P=0.008, n P<0.001). The results indicated that FBXW7 mutated tumors had stronger immunogenicity, which might generate anti-tumor immunity. FBXW7 mutation was also related to the activation of T cells (T lymphocyte receptor complexes and signaling). In addition, FBXW7 mutation was correlated with increased infiltration of CD8n +T cells and M1 macrophages. CD8n +T cells and M1 macrophages infiltration level was significantly up-regulated in FBXW7 mutation group than wild-type group [10% (8%, 14%) vs 7%(4%, 12%), n P=0.049; 8%(4%, 11%) vs 4%(1%, 8%), n P=0.046].n Conclusions:NSCLC patients with FBXW7 mutant have higher clinical benefits from immunotherapy. FBXW7 mutation has the potential as a predictive marker for the efficacy of immunotherapy in NSCLC patients.