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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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          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.

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          Most cited references17

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          Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer

          We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached. Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab. (Funded by Merck; KEYNOTE-001 ClinicalTrials.gov number, NCT01295827.).
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            Approaches to treat immune hot, altered and cold tumours with combination immunotherapies

            Immunotherapies are the most rapidly growing drug class and have a major impact in oncology and on human health. It is increasingly clear that the effectiveness of immunomodulatory strategies depends on the presence of a baseline immune response and on unleashing of pre-existing immunity. Therefore, a general consensus emerged on the central part played by effector T cells in the antitumour responses. Recent technological, analytical and mechanistic advances in immunology have enabled the identification of patients who are more likely to respond to immunotherapy. In this Review, we focus on defining hot, altered and cold tumours, the complexity of the tumour microenvironment, the Immunoscore and immune contexture of tumours, and we describe approaches to treat such tumours with combination immunotherapies, including checkpoint inhibitors. In the upcoming era of combination immunotherapy, it is becoming critical to understand the mechanisms responsible for hot, altered or cold immune tumours in order to boost a weak antitumour immunity. The impact of combination therapy on the immune response to convert an immune cold into a hot tumour will be discussed.
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              Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

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                Author and article information

                Journal
                Transl Lung Cancer Res
                Transl Lung Cancer Res
                TLCR
                Translational Lung Cancer Research
                AME Publishing Company
                2218-6751
                2226-4477
                June 2021
                June 2021
                : 10
                : 6
                : 2858-2864
                Affiliations
                [1 ]deptDepartment of Respiratory Medicine , Royal Melbourne Hospital , Parkville, Victoria, Australia;
                [2 ]deptDepartment of Medicine , University of Melbourne , Parkville, Victoria, Australia;
                [3 ]deptDepartment of Respiratory Medicine , Austin Hospital , Heidelberg, Victoria, Australia;
                [4 ]Personalised Oncology Division , The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;
                [5 ]deptSchool of Health and Biomedical Sciences , RMIT University , Bundoora, Victoria, Australia;
                [6 ]deptDepartment of Pathology , Royal Melbourne Hospital , Parkville, Victoria, Australia;
                [7 ]Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia;
                [8 ]deptDepartment of Thoracic Surgery , Royal Melbourne Hospital , Parkville, Victoria, Australia
                Author notes
                Correspondence to: Dr. Kanishka Rangamuwa. Respiratory Department, Royal Melbourne Hospital, 300 Grattan St, Parkville, Victoria 3050, Australia. Email: Kanishka.rangamuwa@ 123456mh.org.au .
                Article
                tlcr-10-06-2858
                10.21037/tlcr-21-76
                8264342
                34295683
                58f1f67b-c9d6-487c-a82e-ee39f179fe8d
                2021 Translational Lung Cancer Research. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 31 January 2021
                : 11 May 2021
                Categories
                Brief Report on Lung Cancer and The Immune System

                non-small cell lung cancer (nsclc),thermal ablation,programmed death-ligand 1 (pd-l1),cancer immunity

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