Peripheral Circulating Blood Cells Deviation Based on Tumor Inflammatory Microenvironment Activity in Resected Upstaged Lung Adenocarcinomas

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: Preoperatively, the TIME-a group demonstrated a significantly higher lymphocyte count (<i>p</i> = 0.02) and a lower absolute neutrophil rate (<i>p</i> = 0.01) than TIME-s. These differences persisted after resection (<i>p</i> = 0.06 and <i>p</i> = 0.02) while they became similar one month after surgery (<i>p</i> = 1 and <i>p</i> = 0.32). The neutrophil-to-lymphocyte ratio-NLR showed similar trends (<i>p</i> = 0.01 and <i>p</i> = 1). Better OS and RFS were shown in the TIME-a group (<i>p</i> = 0.02 and 0.03, respectively). <b>Conclusions</b>: 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.