Department of Anesthesiology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Ann Surg Oncol. 2024 Dec;31(13):9332-9343. doi: 10.1245/s10434-024-16053-7. Epub 2024 Aug 27.
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.
免疫检查点抑制剂（ICIs）的新辅助免疫治疗已经彻底改变了早期非小细胞肺癌（NSCLC）的治疗方式。然而，对于哪些患者最有可能从新辅助免疫治疗中获益，目前知之甚少。在这项研究中，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，以探索与免疫反应相关的分子特征。
共纳入 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检测、外周血 bulk TCR 测序和多重免疫组化分析。
基线时基质细胞衍生因子（SDF）-1alpha 水平较低与无病生存（DFS）不良相关。在接受新辅助免疫治疗一个周期后，伴有主要病理缓解（MPR）的患者 HGF 水平下降。在接受新辅助免疫治疗后发生免疫相关不良事件（irAE）的患者中观察到 IDO 和 IP-10 增加。irAE 与 MPR 或 DFS 之间无相关性。MPR 组在新辅助免疫治疗后白细胞和中性粒细胞计数显著下降。新辅助免疫治疗前外周血 TCR 收敛度高与肺鳞癌（LUSC）患者的 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 细胞浸润显著增加。
本研究提示细胞因子和 TCR 收敛度在预测可切除 NSCLC 和 LUSC 中 ICIs 反应方面具有潜在作用。CD8+CD39+T 细胞和 CD4+T 细胞可能参与新辅助免疫治疗的作用。
