Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
The Medical Department, 3D Medicines Inc., Shanghai, China.
Ann Surg Oncol. 2023 Nov;30(12):7549-7560. doi: 10.1245/s10434-023-14123-w. Epub 2023 Aug 16.
Neoadjuvant chemoimmunotherapy treatment (NCIT) has achieved great success for non-small cell lung cancer (NSCLC); however, the intrinsic mechanism underlying this treatment remains unclear.
Thirty-two patients with stage IIA-IIIC NSCLC who underwent surgery after NCIT were included in this retrospective study. Multiplex immunofluorescence (mIF) staining and image analysis assays were performed on the samples collected before and after NCIT for each patient. RNA analyses was applied to confirm the mIF results.
Among the enrolled patients, 14 achieved major pathological response or pathological complete response (pCR) and were defined as the 'response' group, whereas 18 patients did not respond well to NCIT and were defined as the 'nonresponse' group. The results of the mIF assays revealed an overall increase in tumor immune lymphocytes (TILs) after NCIT in the stroma area (p = 0.03) rather than the tumor area (p = 0.86). The percentage of CD8+ T cells and tertiary lymphoid structure counts in both the response and nonresponse groups increased significantly after NCIT compared with before NCIT. CD3+ T cells and FOXP3+ cells decreased significantly in the response group but remained unchanged or increased in the nonresponse group. A comparison of the response and nonresponse groups showed that CD3, FOXP3+ and CD8+/PD-1+ cells before NCIT may serve as predictors of the response to neoadjuvant immunotherapy. The RNA analyses confirmed the mIF results that TILs were elevated after NCIT.
The infiltration of immune cells before NCIT was correlated with pathologic complete response, which enhanced the TILs as a promising predictor for selecting patients who were more likely to benefit from NCIT.
新辅助化疗免疫治疗（NCIT）已在非小细胞肺癌（NSCLC）中取得巨大成功，但这种治疗的内在机制尚不清楚。
本回顾性研究纳入了 32 例接受 NCIT 后手术的 IIA-IIIC 期 NSCLC 患者。对每位患者的 NCIT 前后样本进行了多重免疫荧光（mIF）染色和图像分析检测，同时进行了 RNA 分析以验证 mIF 结果。
在纳入的患者中，14 例患者获得了主要的病理缓解或病理完全缓解（pCR），定义为“缓解”组，而 18 例患者对 NCIT 反应不佳，定义为“非缓解”组。mIF 检测结果显示，NCIT 后肿瘤间质区的肿瘤免疫淋巴细胞（TILs）总体增加（p=0.03），而肿瘤区无明显变化（p=0.86）。与 NCIT 前相比，缓解组和非缓解组的 CD8+T 细胞和三级淋巴结构计数均显著增加。缓解组的 CD3+T 细胞和 FOXP3+细胞显著减少，而非缓解组则保持不变或增加。缓解组和非缓解组之间的比较显示，NCIT 前的 CD3、FOXP3+和 CD8+/PD-1+细胞可能是预测新辅助免疫治疗反应的指标。RNA 分析证实了 mIF 结果，即 NCIT 后 TILs 增加。
NCIT 前免疫细胞的浸润与病理完全缓解相关，增强了 TILs 作为选择更有可能从 NCIT 中获益的患者的有前途的预测指标。
