Integrating cryoablation with immunotherapy in non-small cell lung cancer: mechanisms, clinical evidence, and translational barriers.

Authors

Chulan Yang, Xinan Long, Yangyang Ma, Lizhi Niu

Published in

Frontiers in oncology. Volume 16. Pages 1869239. Epub Jul 31, 2026.

Abstract

Despite major advances in targeted therapy and immune checkpoint blockade, advanced NSCLC still has poor long-term outcomes. Only a minority of patients achieve durable benefit, and many eventually experiencing disease progression. Local ablation techniques, particularly cryoablation, directly destroy tumors and remodel the local immune microenvironment by inducing immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns (DAMPs). These processes may contribute to systemic antitumor immunity and are associated with a more inflamed tumor immune microenvironment. This review summarizes the biological mechanisms underlying the potential synergy between cryoablation and immunotherapy, particularly immune checkpoint inhibitors. Cryoablation has been proposed to act as an in situ vaccination strategy by preserving native tumor antigens and enhancing antigen presentation and T-cell priming. These effects may in turn trigger systemic antitumor immune responses beyond the treated site. The article summarizes preclinical and clinical evidence supporting this combined approach. Available studies suggest that cryoablation combined with immunotherapy may improve tumor control and survival outcomes in selected NSCLC settings. However, current clinical evidence remains heterogeneous and is still limited in scale. Finally, we discuss key challenges, including treatment sequencing, biomarker development, technical standardization, and long-term safety, and outline future directions for prospective and biomarker-informed clinical studies. This review highlights the potential role of cryoablation as an adjunct to immunotherapy in selected NSCLC settings, while emphasizing the need for further prospective validation.

PMID:
42602485
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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