Serial monitoring of the Inflammatory Response in Resectable Lung Cancer

Abstract

Background: The perioperative period in non-small cell lung cancer (NSCLC) represents a critical window during which surgical stress, tumour biology, and host immunity interact, influencing post-operative complications and long-term outcomes. Understanding how immune cell populations, immune checkpoint proteins, and systemic inflammatory indexes change perioperatively may reveal predictive biomarkers for complications and disease recurrence.

Methods: This longitudinal study of NSCLC patients undergoing lung resection, integrates analyses of adaptive and innate immune cell populations, inhibitory checkpoint protein expression and systemic inflammatory indexes. Samples were collected at baseline and multiple post-operative timepoints (2–4 days and 6–9 weeks). Associations between immune parameters, post-operative complications, and disease-free survival (DFS) were evaluated using regression and Cox proportional hazards models, adjusting for clinical covariates.

Results: Early post-operative inflammatory indexes (Neutrophil-to-Lymphocyte ratio >4.9, Systemic Immune-Inflammatory Index >1050, Systemic Inflammatory Response Index >4) were predictive of post-operative complications. Immune profiles associated with post-operative complications included higher central memory CD4+ T cells, reduced CD8+ naïve T cells, and mucosal associated invariant (MAIT) cells. Perioperative expansion were observed in CD8+ T cells, CD4+ regulatory T cells, Natural Killer (NK), NKT-like, and MAIT cells. Surgery induced upregulation of inhibitory checkpoints across multiple cell types. Dynamic longitudinal changes in CD4+ central memory T cells, CD8+ naïve and effector memory T cells, B cells, NK cells, and checkpoint co-expression, baseline Haemoglobin Albumin Lymphocyte index (>54) and Prognostic Nutritional Index (>56) were independently associated with disease free survival. Advanced disease stage, tumour histology, age, and post-operative complications modulated these immune dynamics.

Conclusions: This study demonstrates that surgical resection in NSCLC induces dynamic immune changes, with longitudinal monitoring having the potential to inform risk stratification and prognosis. Integrating immune profiling into postoperative care offers a minimally invasive approach to guide surveillance, tailor interventions, and mitigate recurrence risk. These findings highlight the potential of perioperative immunological assessment to optimize personalized management and improve long-term outcomes in lung cancer.