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A team of DZL researchers at the Translational Lung Research Center Heidelberg (TLRC) has explored the effectiveness of pembrolizumab, an immunotherapy drug, before surgery in treating non-small cell lung cancer (NSCLC). The results of the NEOMUN study, recently published in the Journal for ImmunoTherapy of Cancer, demonstrate that pembrolizumab as a monotherapy is not only safe but can also significantly reduce tumor growth in some patients before surgery, thereby likely improving progression-free survival.
The study involved 29 participants with operable stage II or IIIA NSCLC. Some patients showed particularly strong responses to treatment. In about a quarter of the cases, the tumor was almost entirely destroyed after treatment, and in some instancescases, no active tumor could be detected at all. Surgery was successfully completed in every all cases. Even after three years, more than 80% precent of the patients were still alive, with three-quarters of them remaining free of disease recurrence.
Checkpoint inhibitors like pembrolizumab are crucial because they release a "brake" on the immune system, allowing the body’s own defense cells to more effectively recognize and fight cancer cells more effectively.
The researchers also identified potential biomarkers that could predict a favorable response to treatment. A high tumor mutational burden and strong PD-L1 protein activity were both linked to better treatment outcomes. In the future, Tthese biomarkers could , in the future, help personalize treatment plans.
Of particular interest are new findings about the tumor microenvironment— the network of cells surrounding the tumor. Analyses presented at the World Conference on Lung Cancer revealed that in cases with the strongest therapeutic responses, there was a notable presence of active CD8-positive T cells that specifically target cancer cells. Additionally, certain B cells and other immune cells were more abundant. In contrast, tumors that did not respond to treatment had compositions similar to resembled untreated control samples in their composition.
“Immunotherapy has become the standard of care for many patients before lung cancer surgery, thanks to numerous positive study results. By thoroughly analyzing the blood and tissue samples collected in the NEOMUN study, we hope to gain deeper insights into how the immune system responds to successful therapy before surgery, and what conditions are needed for optimal results,” says Prof. Martin Eichhorn, principal investigator of the trial at the Thoraxklinik of Heidelberg University Hospital. “This could lead to more individualized and effective treatment approaches, minimizing therapy-related side effects and potentially reducing the extent of surgery required.”
Alongside the team at TLRC Heidelberg, Prof. Rajkumar Savai, Professor at the Institute of Lung Research (ILH) at Justus Liebig University (JLU) in Gießen, contributed to the study. He serves as the Scientific Director of the DZL Lung Cancer Research Program.
In close collaboration with the National Center for Tumor Disease Heidelberg and the German Cancer Research Center, further research is underway. Using advanced multiomics techniques, the team aims to better understand the complex changes in the immune microenvironment and identify new predictive markers for treatment success.
Source: Immunotherapy before lung cancer surgery shows promising results - TLRC Heidelberg
Original Publications: Eichhorn ME, Niedermaier B, Charoentong P et al. Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial. J Immunother Cancer. 2025 Aug 4;13(8):e011874. doi: 10.1136/jitc-2025-011874.
Niedermaier B, Charoentong P, Zoernig I et al. Abstract MA04.06 Neoadjuvant Pembrolizumab: Multi-Omics Characterization of the Tumoral Immune Response Reveals Distinct Mechanisms of Action. IASLC 2025 World Conference on Lung Cancer.
