Bonis Alessandro, Lunardi Francesca, Pagliarini Giulia, Verzeletti Vincenzo, Lione Luigi, Busetto Alberto, Cannone Giorgio, Comacchio Giovanni Maria, Mammana Marco, Faccioli Eleonora, Rebusso Alessandro, Schiavon Marco, Nicotra Samuele, Dell'Amore Andrea, Rea Federico
Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health-DSCTV, University of Padova, 35128 Padova, Italy.
Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health-DSCTV, University of Padova, 35128 Padova, Italy.
J Clin Med. 2024 Dec 13;13(24):7597. doi: 10.3390/jcm13247597.
: The tumour inflammatory microenvironment (TIME) reflects a selective activation of the central immune system (IS), particularly T-cells expansion, which leads to immune cells migrating to the target, such as lung cancer, via the bloodstream and lymphatic vessels. In this study, the aim is to investigate whether the distribution of peripheral blood cells varies based on the immune status of patients with lung adenocarcinoma. : This is a single-center retrospective study conducted in the Thoracic Surgery Unit of the University of Padua (Italy) between 1 January 2016 and 1 April 2024. It included patients (>18 years old) with lung adenocarcinoma deemed resectable (cT2bN0M0 or lower) who experienced pathological upstaging (IIB or higher). Patients were classified as TIME-active (with tumour-infiltrating lymphocytes-TILs and/or PD-L1 expression) or TIME-silent (without TILs or PD-L1). According to the TIME status, peripheral blood cell counts with clinical and pathological data were compared between groups using the Fisher's, Pearson's or Wilcoxon's test when appropriate. A Kaplan-Meier estimator investigated overall survival (OS) and recurrence-free survival (RFS) adopting the log-rank test. : Preoperatively, the TIME-a group demonstrated a significantly higher lymphocyte count ( = 0.02) and a lower absolute neutrophil rate ( = 0.01) than TIME-s. These differences persisted after resection ( = 0.06 and = 0.02) while they became similar one month after surgery ( = 1 and = 0.32). The neutrophil-to-lymphocyte ratio-NLR showed similar trends ( = 0.01 and = 1). Better OS and RFS were shown in the TIME-a group ( = 0.02 and 0.03, respectively). : Resected upstaged lung adenocarcinomas show distinct peripheral blood cell profiles based on immune status. TIME-active patients had a significantly lower NLR, which normalized post-surgery. Surgical resection may help restore native immune surveillance.
肿瘤炎性微环境（TIME）反映了中枢免疫系统（IS）的选择性激活，尤其是T细胞的扩增，这会导致免疫细胞通过血液和淋巴管迁移至靶标，如肺癌。在本研究中，目的是调查外周血细胞的分布是否会因肺腺癌患者的免疫状态而有所不同。
这是一项在意大利帕多瓦大学胸外科进行的单中心回顾性研究，时间跨度为2016年1月1日至2024年4月1日。研究纳入了年龄大于18岁、被认为可切除（cT2bN0M0或更低）但病理分期上调（IIB或更高）的肺腺癌患者。患者被分为TIME激活型（有肿瘤浸润淋巴细胞-TILs和/或PD-L1表达）或TIME沉默型（无TILs或PD-L1）。根据TIME状态，在适当情况下，使用Fisher检验、Pearson检验或Wilcoxon检验对组间的外周血细胞计数与临床和病理数据进行比较。采用Kaplan-Meier估计器，并通过对数秩检验研究总生存期（OS）和无复发生存期（RFS）。
术前，TIME激活组的淋巴细胞计数显著高于TIME沉默组（P = 0.02），绝对中性粒细胞率低于TIME沉默组（P = 0.01）。这些差异在切除后仍然存在（P = 0.06和P = 0.02），而在术后1个月时变得相似（P = 1和P = 0.32）。中性粒细胞与淋巴细胞比值-NLR显示出相似的趋势（P = 0.01和P = 1）。TIME激活组的OS和RFS表现更好（分别为P = 0.02和0.03）。
切除的分期上调肺腺癌根据免疫状态显示出不同的外周血细胞特征。TIME激活型患者的NLR显著更低，术后恢复正常。手术切除可能有助于恢复天然免疫监视。
