Early Immune Shifts May Predict Immunotherapy Success in NSCLC

By: Noah Levine
Posted: Tuesday, February 25, 2025

Immunotherapy offers new approaches for treatment of non–small cell lung cancer (NSCLC), but patients’ immune systems react differently to these treatments, and a deeper understanding of these immune responses may help to tailor treatment to each individual’s needs. In a study published in Frontiers in Immunology, Chiara Napoletano, PhD, of Sapienza University of Rome, and colleagues identified several early immune responses to anti–PD-1 therapy that may serve as biomarkers to predict patient outcomes, although future research with larger patient cohorts is needed to validate these findings.

“We have demonstrated that CD137+ T-cell subsets, Treg/CD137+ T-cell ratio, and [soluble] LAG3 evaluated at baseline could be considered potential predictive biomarkers of response to therapy,” Dr. Napoletano and colleagues wrote. “These results could have a relevant impact in the clinical setting where the PD-L1 expressed by the tumor tissue represents the only biomarker to select the best therapeutic choice for NSCLC patients.”

The study analyzed immune responses in 48 patients with metastatic nononcogene-addicted NSCLC treated with immune checkpoint inhibitors, including pembrolizumab and nivolumab. Researchers evaluated immune cell subsets and soluble immune checkpoints before treatment (T0) and after the first cycle (T1) using cytofluorimetry and multiplex assays.

They observed a significant increase in proliferating Ki67 plus CD8+ T cells following treatment, suggesting immunotherapy stimulates cytotoxic T-cell expansion, which could play a crucial role in tumor control. Of note, this increase was more pronounced in patients who responded to treatment. Although active regulatory T cells (Tregs) decreased, nonsuppressive Tregs increased during therapy, particularly in responding patients. This shift in immune balance suggests that successful immunotherapy may tilt the immune system toward activation rather than suppression.

Responding patients maintained higher levels of CD137+ T cells, a marker of T-cell activation and survival. Additionally, an increase in soluble PD-1 and lower baseline levels of soluble LAG3 seemed to be associated with better responses to immune checkpoint inhibitors.

Disclosure: For full disclosures of the study authors, visit frontiersin.org.

Frontiers in Immunology

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