使用免疫检查点抑制剂（ICIs）的新辅助免疫疗法彻底改变了早期非小细胞肺癌（NSCLC）的治疗。然而，对于哪些患者可能从新辅助免疫治疗中获益最多，人们知之甚少。在本研究中，我们对接受新辅助免疫治疗的可切除 NSCLC 样本进行了多平台分析，以探讨与免疫反应相关的分子特征。总共纳入了 17 例接受新辅助免疫治疗的可切除 IB-IIIA 期 NSCLC 患者。进行了多重细胞因子测定、外周血中的大量 TCR 测序和多重免疫组织化学。基线时低水平的基质细胞衍生因子 (SDF)-1α 与不利的无病生存 (DFS) 相关。具有主要病理反应（MPR）的患者在新辅助免疫治疗一个周期后显示 HGF 下降。在新辅助免疫治疗后出现免疫相关不良事件 (irAE) 的患者中观察到 IDO 和 IP-10 增加。 irAE 与 MPR 或 DFS 之间没有相关性。新辅助免疫治疗后，MPR 组白细胞和中性粒细胞计数显着下降。在接受新辅助免疫治疗的肺鳞状细胞癌 (LUSC) 中，高外周基线 TCR 收敛与 MPR 和良好的 DFS 相关。新辅助免疫治疗导致肿瘤区域 CD4、CD8 和 CD8 CD39 T 细胞浸润显着增加。这项研究表明细胞因子和 TCR 收敛在预测可切除 NSCLC 和 LUSC 中 ICI 反应方面的潜在作用。 CD8 CD39 T 细胞和 CD4 T 细胞可能参与新辅助免疫治疗的作用。© 2024。外科肿瘤学会。

Neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of early stage non-small cell lung cancer (NSCLC). However, little is known about which patients are likely to benefit most from neoadjuvant immunotherapy. In this study, we performed a multiplatform analysis on samples from resectable NSCLC treated with neoadjuvant immunotherapy to explore molecular characteristics related to immune responses.A total of 17 patients with resectable stage IB-IIIA NSCLC treated with neoadjuvant immunotherapy were included. A multiplex cytokine assay, bulk TCR sequencing in peripheral blood, and multiplexed immunohistochemistry were performed.Low levels of stromal cell-derived factor (SDF)-1alpha at baseline were associated with unfavorable disease-free survival (DFS). Patients with major pathologic response (MPR) showed a decrease in HGF after one cycle of neoadjuvant immunotherapy. An increase in IDO and IP-10 was observed in patients who developed immune-related adverse events (irAEs) after neoadjuvant immunotherapy. There were no correlations between irAEs and MPR or DFS. The MPR group presented a significant decrease in white blood cells and neutrophil count after neoadjuvant immunotherapy. The high peripheral baseline TCR convergence was correlated with MPR and favorable DFS in lung squamous cell carcinoma (LUSC) receiving neoadjuvant immunotherapy. Neoadjuvant immunotherapy led to a significant increase in CD4+, CD8+, and CD8+CD39+ T-cell infiltration in tumor areas.This study suggests the potential roles of cytokines and TCR convergence for predicting ICIs response in resectable NSCLC and LUSC. CD8+CD39+T cells and CD4+ T cells could be involved in the action of neoadjuvant immunotherapy.© 2024. Society of Surgical Oncology.