新辅助免疫疗法已被证明对可切除的非小细胞肺癌（NSCLC）患者有效且安全。然而，不同致癌驱动突变的存在可能会影响肿瘤微环境，从而影响免疫治疗的临床获益。 这项回顾性研究纳入了连续接受单次大容量新辅助免疫治疗后接受根治性手术的 NSCLC 患者（IIA 至 IIIB 期）中心于2019年12月至2022年8月期间进行。根据驱动癌基因状态比较病理反应和长期结果，并进行RNA测序分析以调查治疗前后的转录组特征。在本研究纳入的167名患者中，47名患者具有致癌驱动突变。在 28 名患者中发现了 KRAS 驱动突变，占致癌驱动突变的 59.6%。其中，17例患者出现主要病理反应，显着高于非KRAS驱动突变组（60.7% vs. 31.6%，P = 0.049）。多变量Cox回归分析进一步显示，KRAS驱动突变组是延长无病生存期的独立预后因素（风险比：0.10，P = 0.032）。 KRAS 驱动突变 NSCLC 中 CD8 T 细胞的中位比例显着高于非驱动突变组（18% vs. 13%，P = 0.030）。此外，免疫相关通路在 KRAS 驱动突变 NSCLC 中富集，并在免疫治疗后激活。我们的研究表明，具有 KRAS 驱动突变的 NSCLC 患者对新辅助免疫治疗具有优异的反应，可能是由于其较高的免疫原性。这些发现强调了在为 NSCLC 患者选择新辅助治疗策略时考虑致癌驱动突变的重要性。© 2023。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

Neoadjuvant immunotherapy has been demonstrated to be effective and safe in resectable non-small cell lung cancer (NSCLC) patients. However, the presence of different oncogenic driver mutations may affect the tumor microenvironment and consequently influence the clinical benefit from immunotherapy.This retrospective study included consecutive NSCLC patients (stage IIA to IIIB) who underwent radical surgery after receiving neoadjuvant immunotherapy at a single high-volume center between December 2019 and August 2022. Pathological response and long-term outcomes were compared based on the driver oncogene status, and RNA sequencing analysis was conducted to investigate the transcriptomic characteristics before and after treatment.Of the 167 patients included in this study, 47 had oncogenic driver mutations. KRAS driver mutations were identified in 28 patients, representing 59.6% of oncogenic driver mutations. Of these, 17 patients had a major pathological response, which was significantly higher than in the non-KRAS driver mutation group (60.7% vs. 31.6%, P = 0.049). Multivariate Cox regression analysis further revealed that the KRAS driver mutation group was an independent prognostic factor for prolonged disease-free survival (hazard ratio: 0.10, P = 0.032). The median proportion of CD8+ T cells was significantly higher in the KRAS driver mutation NSCLCs than in the non-driver mutation group (18% vs. 13%, P = 0.030). Furthermore, immune-related pathways were enriched in the KRAS driver mutation NSCLCs and activated after immunotherapy.Our study suggests that NSCLC patients with KRAS driver mutations have a superior response to neoadjuvant immunotherapy, possibly due to their higher immunogenicity. The findings highlight the importance of considering oncogenic driver mutations in selecting neoadjuvant treatment strategies for NSCLC patients.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.