INTRODUCTION Immune checkpoint inhibitors are highly effective in treating various cancers. We analyzed the significance of the KRAS/STK11 co-mutation in relation to the efficacy of immune checkpoint inhibitors in pan-cancer patient cohort. METHODS We analyzed data from open-access research: MSK-IMPACT (molecular profiling data from patients receiving systemic antitumor therapy) and MSK-TMB (molecular profiling data from patients receiving immune checkpoint inhibitors). In both studies, high throughput sequencing was used for molecular profiling. RESULTS A total of 10,336 patients receiving antitumor therapy (MSK-IMPACT study) and 1661 patients receiving immune checkpoint inhibitors (MSK-TMB study) were included in the analysis. Co-mutation STK11/KRAS was found in 156 (1.5%) and 46 (2.8%) patients in the two studies, respectively. Most patients with the STK11/KRAS co-mutation had non-small cell lung cancer (83% and 85% in the two studies, respectively). Among non-small cell lung cancer patients, the STK11 mutation was associated with a worse outcome for patients receiving systemic antitumor therapy, but not immune checkpoint inhibition therapy (HR for OS 1.90 [95% CI 1.36-2.65] and 1.44 [95% CI 0.88-2.37]). Co-mutation STK11/KRAS was also not associated with patient outcome in any of the studies (HR for OS 0.93 [95% CI 0.56-1.52] and 1.09 [95% CI 0.54-2.19]). High tumor mutational burden was associated with better outcome in the cohort of patients receiving immune checkpoint inhibitors. An analogous analysis among patients in the pan-cancer cohort (excluding patients with non-small cell lung cancer) showed STK11 mutations and high tumor mutational burden have a predictive role for the efficacy of immune checkpoint inhibitors, but not STK11/KRAS co-mutation. CONCLUSIONS Co-mutation STK11/KRAS is common among patients with non-small cell lung cancer and is not an independent predictive marker for the efficacy of immune checkpoint inhibitors. Further studies are required to clarify the role of STK11 mutations in immune checkpoint inhibitor treatment response.

中文翻译：

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STK11/KRAS 共突变对现实世界泛癌症队列中免疫治疗反应的影响。

简介 免疫检查点抑制剂对于治疗各种癌症非常有效。我们分析了 KRAS/STK11 共突变与泛癌患者队列中免疫检查点抑制剂疗效的关系的重要性。方法 我们分析了来自开放获取研究的数据：MSK-IMPACT（接受全身抗肿瘤治疗的患者的分子分析数据）和 MSK-TMB（接受免疫检查点抑制剂的患者的分子分析数据）。在这两项研究中，都使用高通量测序进行分子分析。结果 分析中总共纳入了 10,336 名接受抗肿瘤治疗的患者（MSK-IMPACT 研究）和 1661 名接受免疫检查点抑制剂的患者（MSK-TMB 研究）。这两项研究分别在 156 名 (1.5%) 和 46 名 (2.8%) 患者中发现了 STK11/KRAS 共突变。大多数 STK11/KRAS 共突变患者患有非小细胞肺癌（两项研究中分别为 83% 和 85%）。在非小细胞肺癌患者中，STK11 突变与接受全身抗肿瘤治疗的患者的较差结局相关，但与接受免疫检查点抑制治疗的患者无关（OS 的 HR 为 1.90 [95% CI 1.36-2.65] 和 1.44 [95% CI 0.88-2.37]）。在任何研究中，STK11/KRAS 共突变也与患者结果无关（OS 的 HR 0.93 [95% CI 0.56-1.52] 和 1.09 [95% CI 0.54-2.19]）。在接受免疫检查点抑制剂的患者队列中，高肿瘤突变负荷与更好的结果相关。对泛癌队列患者（不包括非小细胞肺癌患者）进行的类似分析显示，STK11 突变和高肿瘤突变负荷对免疫检查点抑制剂的疗效具有预测作用，但 STK11/KRAS 共突变没有预测作用。结论 STK11/KRAS 共突变在非小细胞肺癌患者中很常见，并不是免疫检查点抑制剂疗效的独立预测标志物。需要进一步的研究来阐明 STK11 突变在免疫检查点抑制剂治疗反应中的作用。