Department of Medicine V, Member of the German Center for Lung Research, University Hospital, Ludwig Maximilians University (LMU) Munich, Munich, Germany.
Department of Thoracic Surgery, Thoracic Oncology Centre Munich, University Hospital, Ludwig Maximilians University (LMU) Munich, Munich, Germany.
Front Immunol. 2022 Jun 27;13:858212. doi: 10.3389/fimmu.2022.858212. eCollection 2022.
Tumor tissue as well as regional lymph nodes are removed during curative surgery for early-stage non-small cell lung cancer (NSCLC). These tissues provide a unique snapshot of the immune cell composition at the time of surgery. We investigated the immune landscape in matched tumor tissue, tumor bearing (tb) and non-tumor bearing (ntb) N1 as well as N2 lymph nodes (LNs) in patients with NSCLC and its relation to survival.
Internal hospital databases were screened for surgically treated NSCLC patients for whom tumor tissue, tbLNs as well as N1 and N2 ntbLNs were available. Clinical as well as demographic data were extracted from hospital records. Expression profiling of 770 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies.
We identified 190 surgically treated patients of whom 16 fulfilled inclusion criteria and had sufficient archived tissue. The Tumor Immune Dysfunction and Exclusion (TIDE) score in N1 tumor-free lymph nodes was associated with OS. TIM-3 expression was inversely correlated with TIDE scores in affected LNs, N1 and N2 ntbLNs. Levels of CD8 expression were significantly higher in TIDE High compared to TIDE Low patients. TIM-3 and PD-L1 were selected for the final model for OS in multivariate regression in more than one tissue.
Levels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC.
在早期非小细胞肺癌（NSCLC）的根治性手术中，会切除肿瘤组织和局部淋巴结。这些组织在手术时提供了免疫细胞组成的独特快照。我们研究了 NSCLC 患者匹配的肿瘤组织、肿瘤携带（tb）和非肿瘤携带（ntb）N1 以及 N2 淋巴结（LNs）中的免疫景观及其与生存的关系。
从内部医院数据库中筛选出接受过手术治疗的 NSCLC 患者，这些患者有肿瘤组织、tbLNs 以及 N1 和 N2 ntbLNs。从医院记录中提取临床和人口统计学数据。使用 NanoString Technologies 的 PanCancer IO 360 面板对 770 个免疫相关基因进行表达谱分析。
我们确定了 190 名接受手术治疗的患者，其中 16 名符合纳入标准并有足够的存档组织。N1 无肿瘤淋巴结中的肿瘤免疫功能障碍和排除（TIDE）评分与 OS 相关。TIM-3 的表达与受影响的 LNs、N1 和 N2 ntbLNs 中的 TIDE 评分呈负相关。TIDE High 组的 CD8 表达水平明显高于 TIDE Low 组。在多变量回归中，TIM-3 和 PD-L1 在两种以上组织中被选择用于 OS 的最终模型。
免疫细胞耗竭标志物的水平可能表明免疫功能障碍，并与 NSCLC 根治性手术后的生存相关。
