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Increase in tumour PD-L1 expression in non-small cell lung cancer following bronchoscopic thermal vapour ablation.

ABSTRACT: Limited early evidence indicates thermal ablation of non-small cell lung cancer (NSCLC) may induce alterations to the immune response that could enhance the efficacy of immunotherapy with immune checkpoint inhibitor therapy. This study reports pilot data demonstrating increased programmed death-ligand 1 (PD-L1) expression on tumour cells in response to bronchoscopic thermal vapour ablation. Five patients underwent bronchoscopic thermal vapour ablation under a treat-and-resect protocol, as part of a clinical safety and feasibility study, with lobectomy performed five days after thermal vapour ablation. PD-L1 (clone SP263) immunohistochemistry (IHC) tumour proportion score (TPS) was assessed on both baseline diagnostic biopsy specimens, and post-ablation resection specimens in five patients with stage I NSCLC. Two areas of the resection sample defined as viable tumour and injured tumour were examined. All tumours demonstrated 0% PD-L1 TPS at baseline. Three of five (60%) patients demonstrated an increase in PD-L1 TPS in areas of injured tumour to 20%, 30% and 50%. One patient demonstrated an increase in PD-L1 expression in an area of viable tumour to 5%. Changes in PD-L1 expression did not correlate with measures of systemic inflammation. Our findings comprise the first evidence that thermal ablation of NSCLC may induce PD-L1 expression. Further investigation is required to determine the extent of an adaptive immune response, and confirm the potential for augmentation of clinical response to immune check point inhibitor therapy in NSCLC.

SUBMITTER: Rangamuwa K

PROVIDER: S-EPMC8264342 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBronchoscopic lung volume reduction (LVR) could significantly improve pulmonary function and quality of life in patients with emphysema. We aimed to assess the efficacy and safety of bronchoscopic thermal vapor ablation (BTVA) on LVR in patients with emphysema at different stage.MethodsA systematic search of database including PubMed, Embase and Cochrane library was conducted to determine all the studies about bronchoscopic thermal vapor ablation published through Dec 1, 2022. Related searching terms were "lung volume reduction", "bronchoscopic thermal vapor ablation", "bronchial thermal vapor ablation" "BTVA" and "emphysema", "efficacy" and"safety". We used standardized mean difference (SMD) to analyze the summary estimates for BTVA therapy.ResultsWe retrieved 30 records through database search, and 4 trials were selected for meta-analysis, including 112 patients with emphysema. Meta-analysis of the pooled effect showed that levels of forced expiratory volume in 1 s (FEV1), residual volume (RV), total lung capacity (TLC), 6-min walk distance (6MWD) and St George's Respiratory Questionnaire (SGRQ) were significantly improved in patients with emphysema following BTVA treatment between 6 months vs. baseline. Additionally, no significant changes in FEV1, RV, TLC and SGRQ occurred from 3 to 6 months of follow-up except for 6MWD. The magnitude of benefit was higher at 3 months compared to 6 months. The most common complications at 6 months were treatment-related chronic obstructive pulmonary disease (COPD) exacerbations (RR: 12.49; 95% CI: 3.06 to 50.99; p < 0.001) and pneumonia (RR: 9.49; 95% CI: 2.27 to 39.69; p < 0.001).ConclusionsOur meta-analysis provided clinically relevant information about the impact and safety of BTVA on predominantly upper lobe emphysema. Particularly, short-term significant improvement of lung function and quality of life occurred especially within the initial 3 months. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.

Project description:PurposeDespite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error. We therefore developed a PET radiotracer to specifically detect PD-L1 expression in a non-invasive manner, which could be of diagnostic and predictive value.MethodsAnti-PD-L1 (clone 6E11, Genentech) was site-specifically conjugated with DIBO-DFO and radiolabelled with 89Zr (89Zr-DFO-6E11). 89Zr-DFO-6E11 was optimized in vivo by longitudinal PET imaging and dose escalation with excess unlabelled 6E11 in HCC827 tumour-bearing mice. Specificity of 89Zr-DFO-6E11 was evaluated in NSCLC xenografts and syngeneic tumour models with different levels of PD-L1 expression. In vivo imaging data was supported by ex vivo biodistribution, flow cytometry, and IHC. To evaluate the predictive value of 89Zr-DFO-6E11 PET imaging, CT26 tumour-bearing mice were subjected to external radiation therapy (XRT) in combination with PD-L1 blockade.Results89Zr-DFO-6E11 was successfully labelled with a high radiochemical purity. The HCC827 tumours and lymphoid tissue were identified by 89Zr-DFO-6E11 PET imaging, and co-injection with 6E11 increased the relative tumour uptake and decreased the splenic uptake. 89Zr-DFO-6E11 detected the differences in PD-L1 expression among tumour models as evaluated by ex vivo methods. 89Zr-DFO-6E11 quantified the increase in PD-L1 expression in tumours and spleens of irradiated mice. XRT and anti-PD-L1 therapy effectively inhibited tumour growth in CT26 tumour-bearing mice (p < 0.01), and the maximum 89Zr-DFO-6E11 tumour-to-muscle ratio correlated with response to therapy (p = 0.0252).ConclusionPET imaging with 89Zr-DFO-6E11 is an attractive approach for specific, non-invasive, whole-body visualization of PD-L1 expression. PD-L1 expression can be modulated by radiotherapy regimens and 89Zr-DFO-6E11 PET is able to monitor these changes and predict the response to therapy in an immunocompetent tumour model.

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Increase in tumour PD-L1 expression in non-small cell lung cancer following bronchoscopic thermal vapour ablation.

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