State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, and Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, China.
J Immunol Res. 2022 Apr 28;2022:8513747. doi: 10.1155/2022/8513747. eCollection 2022.
Neoadjuvant immunotherapy is promising for locally advanced non-small-cell lung cancer (NSCLC). The immune patterns, as a predictor of PD-1/PD-L1 blockade outcomes, of the primary tumor (PT) and metastatic lymph nodes (mLNs) are unknown.
Multiplex immunofluorescence staining and multispectral imaging were used to evaluate the immune patterns of T cells (CD3+) and cytotoxic T cells (CD8+) in terms of density, location (center of tumor (CT) and invasive margin (IM)), and the PD-L1 expression status of tumor cells and stromal T cells of paired PTs and mLNs in 38 stage III NSCLCs.
The densities of T cells and cytotoxic T cells were correlated between PTs and mLNs at both CT and IM. Higher densities of stromal T cells (S-CD3+) at CT and both S-CD3+ and cytotoxic T cells (S-CD8+) at IM were observed in mLNs compared to PTs, while in tumor compartment, there were no differences in the densities of T cells (T-CD3+) or cytotoxic T cells (T-CD8+). Only the density of stromal PD-L1-positive T cells (S-PD-L1+CD3+) at CT was correlated between PTs and mLNs, while the densities and frequencies of S-PD-L1+CD3+ at CT and IM of mLNs were higher than PTs. Combining positive score discordance of PD-L1 between PTs and mLNs was greater than tumor proportion score. immune patterns of T cells and cytotoxic T cells were different between PTs and mLNs in NSCLC. The heterogeneity of the immune patterns may result in different immune-mediated responses to neoadjuvant immunotherapy in PT and mLNs.
新辅助免疫疗法对局部晚期非小细胞肺癌（NSCLC）有很大的前景。原发肿瘤（PT）和转移性淋巴结（mLN）的免疫模式作为 PD-1/PD-L1 阻断治疗结果的预测因子尚不清楚。
采用多重免疫荧光染色和多光谱成像技术，评估 38 例 III 期 NSCLC 配对的 PT 和 mLN 中肿瘤细胞和基质 T 细胞的 PD-L1 表达状态以及 T 细胞（CD3+）和细胞毒性 T 细胞（CD8+）的密度、位置（肿瘤中心（CT）和侵袭边缘（IM））和免疫模式。
PT 和 mLN 中 CT 和 IM 的 T 细胞和细胞毒性 T 细胞密度均相关。与 PT 相比，mLN 中 CT 的基质 T 细胞（S-CD3+）和 IM 的 S-CD3+和细胞毒性 T 细胞（S-CD8+）的密度较高，而在肿瘤区，T 细胞（T-CD3+）或细胞毒性 T 细胞（T-CD8+）的密度没有差异。仅在 CT 处观察到 PT 和 mLN 之间 S-PD-L1+CD3+基质 T 细胞（S-PD-L1+CD3+）的密度相关，而 mLN 中 CT 和 IM 的 S-PD-L1+CD3+的密度和频率均高于 PT。与肿瘤比例评分相比，PT 和 mLN 之间 PD-L1 阳性评分的不一致性更大。NSCLC 中 PT 和 mLN 之间的 T 细胞和细胞毒性 T 细胞免疫模式不同。免疫模式的异质性可能导致 PT 和 mLN 对新辅助免疫治疗的免疫介导反应不同。
