Association of systemic inflammatory markers and tertiary lymphoid structures with pathological complete response in patients with advanced lung adenocarcinoma receiving preoperative treatment: a retrospective cohort study.

BACKGROUND: The evaluation of immune reactivity within both the tumor microenvironment (TME) and the peripheral system has become a cornerstone in assessing the efficacy of cancer therapies. Pathological complete response (pCR) is widely recognized as a key prognostic indicator following neoadjuvant treatment, yet the immune-related biomarkers predictive of pCR remain incompletely characterized. This study aims to identify and validate specific systemic and local immunological factors associated with pCR in patients undergoing antitumor therapy, thereby facilitating more precise and individualized treatment strategies. METHODS: A total of 216 patients with lung adenocarcinoma scheduled to undergo radical resection of pulmonary carcinoma were retrospectively enrolled. Among them, 19 attained pCR, whereas the other 197 did not (non-pCR). A detailed evaluation of clinicopathological features via a logistic regression model identified the predictors of pCR. Hematoxylin and eosin (HE) staining, multiplex immunofluorescence (mIF), and immunohistochemistry (IHC) were performed to analyze the local immune response, in particular the tertiary lymphoid structure (TLS) features. RESULTS: Multivariate regression results revealed that low systemic inflammation, which could be derived from a combination of decreased systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR), was significantly associated with pCR [odds ratio (OR): 3.26; 95% confidence interval (CI): 1.79-6.58; P=0.04]. Increased TLS density and decreased PD1(+) and CD8(+) cell proportions in the TLS of tumor bed were closely associated with pCR. CONCLUSIONS: The local and systemic immune responses are linked to pCR. In addition, a decrease in the SII + NLR level can independently predict pCR, and certain TLS features are also associated with pCR. Immune responses should be carefully studied to optimize the preoperative treatment of patients with advanced lung adenocarcinoma.