Comprehensive Evaluation of Peripheral Immunodynamics in Advanced Non-Small Cell Lung Cancer Associated to Chemotherapy and Immunotherapy

Abstract

Introduction: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC). Despite significant benefits for some patients, durable responses are limited to 20%–30% of cases, necessitating predictive biomarkers for better therapeutic guidance. While tumor-based markers such as PD-L1 expression and tumor mutational burden offer partial insights, peripheral blood biomarkers have emerged as promising minimally invasive tools for monitoring immune dynamics and predicting outcomes.
Methods: This prospective pilot study analyzed the immune profiles of 51 NSCLC patients across three therapy groups—diagnostic (DX), chemotherapy (CT), and ICI-treated (ICB)—using high-dimensional flow cytometry and advanced computational algorithms. Results: Compared to healthy controls, NSCLC patients exhibited significant alterations in immune subsets, including elevated regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Therapy-specific changes included increased effector and activated T cells (e.g., HLA-DR+CD38+ Th1 cells) and dendritic cell subtypes, particularly cDC2, in the ICB group. In contrast, chemotherapy was associated with heightened Tc2 and activated CD8 T cells.
Importantly, distinct immune signatures correlated with therapeutic outcomes. Non-progressors (stable disease or partial response) under ICB displayed higher levels of switch-memory B cells and cDC1, while progressors showed increased naïve B cells and cDC2. These findings highlight the immunomodulatory effects of different therapies and the potential of peripheral biomarkers for treatment stratification.
Results: This study underscores the need for further validation of peripheral blood biomarkers and their integration into clinical decision-making to optimize NSCLC immunotherapy outcomes.