新辅助化疗（NAC）联合免疫治疗越来越多地用于非小细胞肺癌（NSCLC）。组织驻留记忆 T (TRM) 细胞是对抗癌免疫反应的主要子集。然而，NAC 对 TRM 细胞的免疫调节作用仍不清楚。我们建立了两个 NSCLC 队列，包括接受前期手术（美国）和 NAC 随后手术的患者。除了美国队列 (n = 122) 和 NAC 队列 (n = 141) 与切除样本之间的不配对比较之外，58 个匹配的 NAC 前活检样本可用于配对比较。使用多重免疫荧光，我们对 TRM 细胞 (CD103 CD8 ) 和四个异质 TRM 子集进行了表征，包括初始 TRM1 (PD-1-Tim-3-)、预耗尽 TRM2 (PD-1 Tim-3-)、TRM3 (PD- 1-Tim-3 ) 和最终耗尽的 TRM4 (PD-1 Tim-3 )。定义细胞密度、细胞毒性和两个空间特征来评估 NAC 对 TRM 亚群的影响。 TRM 细胞（尤其是 TRM1）的细胞密度、浸润评分和癌细胞邻近评分

Neoadjuvant chemotherapy (NAC) combined with immunotherapy is increasingly used in non-small cell lung cancer (NSCLC). Tissue-resident memory T (TRM) cells are the primary subset responding to anti-cancer immunity. However, the immunomodulatory effects of NAC on TRM cells remain unknown.We established two NSCLC cohorts including patients undergoing upfront surgery (US) and NAC followed by surgery. Beyond the unpaired comparison between the US cohort (n = 122) and NAC cohort (n = 141) with resection samples, 58 matched pre-NAC biopsy samples were available for paired comparisons. Using multiplex immunofluorescence, we characterized TRM cells (CD103+CD8+) and four heterogeneous TRM subsets, including naive TRM1 (PD-1-Tim-3-), pre-exhausted TRM2 (PD-1+Tim-3-), TRM3 (PD-1-Tim-3+), and terminally exhausted TRM4 (PD-1+Tim-3+). Cell density, cytotoxicity, and two spatial features were defined to evaluate the effect of NAC on TRM subsets.The cell densities, infiltration scores, and cancer-cell proximity scores of TRM cells, especially TRM1&2 subsets, were significantly increased after NAC and associated with better prognosis of patients. In Contrast, no significant change was observed in the TRM4 subset, which was associated with poor prognosis. Besides, the cytotoxicity of TRM subsets was unaltered after NAC. Compared with patients without major pathologic response (MPRs), patients with MPR had higher densities of TRM1&2 subsets and higher cancer-cell proximity scores of TRM2&3 subsets. Furthermore, increased density of CD31 + cancer microvessels was positively associated with both TRM and Tnon-RM cells after NAC.NAC may remodel the cell density and spatial distribution of TRM subsets, which is associated with favorable therapeutic effect and prognosis in patients with NSCLC.© 2024. Springer Nature Switzerland AG.