Anti-cancer immune activation post bronchoscopic thermal ablation in non-small cell lung cancer

Thermal ablation has been shown to induce anti-cancer immune responses in some cancers, which might enhance the efficacy of immunotherapy. This study describes the immune changes in both tumour microenvironment(TME) and blood following bronchoscopic thermal vapour ablation(BTVA) and bronchoscopic radiofrequency ablation(BRFA) in patients with non-small cell lung cancer(NSCLC). Patients with stage I NSCLC undergoing BTVA or BRFA as part of a clinical trial were recruited. All patients proceeded to lobectomy post-ablation. Blood and tissue samples collected pre and post-ablation were analysed. Targeted RNA sequencing & multiplex ion beam imaging(MIBI) of tissue was used to assess TME. Mass cytometry(CyTOF) was performed on blood to assess systemic changes. 10 patients(4-BTVA, 6-BRFA) underwent analysis. Differential gene-level expression analysis showed an increase in genes associated with antigen presentation, including <italic>HLA-DRA, HLA-DRB1, LAMP3</italic>(p<0.05). Functional enrichment analysis showed increased gene ontology(GO) signatures for inflammatory response, leukocyte migration, antigen presentation, and dendritic cell antigen processing and presentation(p<0.05). Increased numbers of CD4+ T cells(p<0.05) and macrophages(p<0.05) was seen within injured tumour. An increase in CD4+ central memory T cells and dendritic cells(p<0.05) was observed in blood. These findings suggest bronchoscopic thermal injury of NSCLC results in increase in antigen presentation within TME with features to suggest activation of a T cell-mediated immune response. Increase CD4+ T cells and Macrophages within only the tumour suggests that this is a tumour-specific response.