Comprehensive evaluation of peripheral immunodynamics in advanced non-small cell lung cancer associated to chemotherapy and immunotherapy

Abstract

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.

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. 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.

This study underscores the need for further validation of peripheral blood biomarkers and their integration into clinical decision-making to optimize NSCLC immunotherapy outcomes.