No. 2 Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing Chest Hospital, Capital Medical University, Beijing, China.
Department of Cancer Research Center, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China.
Lung Cancer. 2024 Nov;197:107991. doi: 10.1016/j.lungcan.2024.107991. Epub 2024 Oct 15.
Neoadjuvant chemoimmunotherapy has the potential to reduce tumor burden, improve the pathological complete response (pCR) rate, and significantly prolong patients' disease-free survival (DFS). However, the treatment's effectiveness varies among NSCLC patients. The immunological mechanisms contributing to tumor regression still require further exploration and elucidation.
The immune status of patients' local tumor microenvironment (TME) before and after neoadjuvant chemoimmunotherapy, their paired pulmonary lymph nodes (11th LNs) after therapy, including infiltrating immune cell densities and their correlations, were analyzed using multiplex immunofluorescence.
Fifty-six NSCLC patients undergoing neoadjuvant chemoimmunotherapy were enrolled and subsequently underwent surgical resection and pathological evaluation. Among these, 19 patients achieved a pCR, 6 patients exhibited a major pathological response (MPR), and 31 patients did not achieve MPR. There were no significant difference in the densities of CD8+ T cell, Treg and Dendritic cell (DC) in patients' TME before neoadjuvant therapy (n = 26, P = 0.091, P = 0.753, P = 0.905, respectively), but after treament, these immune cells' dynamics were significantly different between different response group. CD8+ T cell densities were increased in pCR gourp (P = 0.006), but not in non-pCR group (P = 0.389); the densities of Treg were increased in non-pCR gourp (P = 0.0004), but DC were significantly decreased in non-pCR gourp (P = 0.005). After surgery, the TME were also significantly different: patients achieving pCR typically demonstrated high densities of CD8+ T cell, DC and low densities of Tregs (P = 0.0001, P < 0.0001 and P = 0.0004). The immune status of 11th LNs also exhibited significant differences. DC densities were much higher in pCR patients, whereas Treg in the pCR group were significantly lower than those in the non-pCR group (P = 0.0008 and P = 0.003). Furthermore, the densities of DC in the TME showed a moderate positive correlation with DC in 11th LNs (P = 0.0002), while the densities of Tregs in the TME exhibited a moderate negative correlation with DC densities in 11th LNs (P = 0.03). Patients who had high densities of CD8+ T cell in the resection tissues and DC in the LNs, experienced longer DFS (P = 0.048 and P = 0.024).
Immune cells in both pulmonary LNs and the TME collectively influence the remodeling of the NSCLC patient's TME, thus impacting treatment response and prognosis.
新辅助化疗免疫治疗具有降低肿瘤负担、提高病理完全缓解（pCR）率、显著延长患者无病生存期（DFS）的潜力。然而，这种治疗方法在非小细胞肺癌（NSCLC）患者中的效果存在差异。肿瘤消退的免疫机制仍需要进一步探索和阐明。
采用多重免疫荧光技术分析了 56 例接受新辅助化疗免疫治疗的 NSCLC 患者治疗前后局部肿瘤微环境（TME）和治疗后配对肺门淋巴结（11 区淋巴结）的免疫状态，包括浸润免疫细胞密度及其相关性。
共纳入 56 例接受新辅助化疗免疫治疗的 NSCLC 患者，并随后进行了手术切除和病理评估。其中，19 例患者达到 pCR，6 例患者表现出主要病理缓解（MPR），31 例患者未达到 MPR。在新辅助治疗前（n=26），患者 TME 中 CD8+T 细胞、Treg 和树突状细胞（DC）的密度无显著差异（P=0.091、P=0.753、P=0.905），但治疗后，不同反应组之间这些免疫细胞的动态变化存在显著差异。pCR 组 CD8+T 细胞密度增加（P=0.006），而非 pCR 组则无变化（P=0.389）；非 pCR 组 Treg 密度增加（P=0.0004），而非 pCR 组 DC 密度显著降低（P=0.005）。手术后，TME 也存在显著差异：达到 pCR 的患者通常表现出 CD8+T 细胞、DC 高密度和 Treg 低密度（P=0.0001、P<0.0001 和 P=0.0004）。第 11 区淋巴结的免疫状态也存在显著差异。pCR 患者的 DC 密度明显更高，而 pCR 组的 Treg 则明显低于非 pCR 组（P=0.0008 和 P=0.003）。此外，TME 中 DC 的密度与第 11 区淋巴结中的 DC 密度呈中度正相关（P=0.0002），而 TME 中 Treg 的密度与第 11 区淋巴结中 DC 密度呈中度负相关（P=0.03）。在切除组织中具有高 CD8+T 细胞密度和淋巴结中 DC 密度的患者，DFS 更长（P=0.048 和 P=0.024）。
肺门淋巴结和 TME 中的免疫细胞共同影响 NSCLC 患者 TME 的重塑，从而影响治疗反应和预后。
