The role of bronchoscopic cryoimmunotherapy in non-small cell lung cancer: current evidence and future perspectives.

Lung cancer is the leading cause of cancer deaths, and despite therapeutic advances, recurrence and resistance persist. Local tumor ablation can function as an vaccine, but thermal techniques may disrupt antigen and extracellular matrix integrity, potentially limiting immunogenicity, whereas cryoablation has been shown to preserve tumor antigens and matrix architecture while inducing immunogenic cell death. Bronchoscopic cryoimmunotherapy (BCI) aims to prime antitumor immunity rather than achieve complete tumor eradication. We review preclinical and clinical studies evaluating cryoablation and BCI in non-small cell lung cancer (NSCLC), focusing on immune mechanisms, delivery approaches, and combination with systemic therapies, particularly immune checkpoint inhibitors (ICIs). Preclinical models demonstrate that cryoablation releases danger signals and intact tumor antigens, drives dendritic cell maturation, expands effector CD8+ T cells, and activates STING-dependent type I interferon pathways. Early-phase human studies of BCI monotherapy show systemic immune stimulation, including reductions in the derived neutrophil-to-lymphocyte ratio and expansion of CD8+ effector memory populations. Combination cryoablation-ICI regimens have revealed improved response rates in some cohorts, although clinical outcomes have been limited by small, heterogeneous, and non-randomized studies. BCI is a mechanistically compelling, minimally invasive therapy, but its clinical benefit remains unproven and warrants rigorous randomized evaluation.