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      可切除非小细胞肺癌新辅助免疫治疗研究进展 Translated title: Progress on Neoadjuvant Immunotherapy for Resectable Non-small Cell Lung Cancer

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          Abstract

          近年来，免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）对晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者预后的改善已成为共识，越来越多的临床研究也逐渐证明了免疫治疗对于可切除NSCLC患者的重要价值。然而，目前关于新辅助治疗背景下免疫联合策略的探索、治疗相关副作用、预后生物标志物等问题仍存在争议。本文综述了可切除NSCLC患者新辅助免疫治疗的最新进展，引发了新的思考，并讨论了其在临床应用中的优势及挑战。

          Translated abstract

          In recent years, there has been a consensus regarding the enhancement of prognosis in patients with advanced non-small cell lung cancer (NSCLC) through the utilization of immune checkpoint inhibitors (ICIs). Numerous clinical studies have also demonstrated the substantial value of immunotherapy for resectable NSCLC patients. Nevertheless, there remain controversies surrounding the exploration of immune combination strategies, treatment-related side effects, prognostic biomarkers, as well as other issues in the neoadjuvant therapy setting. Consequently, this article presents a comprehensive overview of the recent advancements in neoadjuvant immunotherapy for resectable NSCLC, stimulating fresh perspectives and delving into its merits and challenges in clinical application.

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          The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.

          Peter Goldstraw, Kari Chansky, John Crowley … (2016)
          The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition.
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            Tumour exosome integrins determine organotropic metastasis

            Ayuko Hoshino, Bruno Costa-Silva, Tang-Long Shen … (2015)
            Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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              Neoadjuvant PD-1 Blockade in Resectable Lung Cancer

              Hok Chan, Franco Verde, Haidan Guo … (2018)
              BACKGROUND Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non–small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade. METHODS In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose. The primary end points of the study were safety and feasibility. We also evaluated the tumor pathological response, expression of programmed death ligand 1 (PD-L1), mutational burden, and mutation-associated, neoantigen-specific T-cell responses. RESULTS Neoadjuvant nivolumab had an acceptable side-effect profile and was not associated with delays in surgery. Of the 21 tumors that were removed, 20 were completely resected. A major pathological response occurred in 9 of 20 resected tumors (45%). Responses occurred in both PD-L1-positive and PD-L1-negative tumors. There was a significant correlation between the pathological response and the pretreatment tumor mutational burden. The number of T-cell clones that were found in both the tumor and peripheral blood increased systemically after PD-1 blockade in eight of nine patients who were evaluated. Mutation-associated, neoantigen-specific T-cell clones from a primary tumor with a complete response on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks after treatment; some of these clones were not detected before the administration of nivolumab. CONCLUSIONS Neoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The tumor mutational burden was predictive of the pathological response to PD-1 blockade. Treatment induced expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood. (Funded by Cancer Research Institute–Stand Up 2 Cancer and others; ClinicalTrials.gov number, NCT02259621.)
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                Author and article information

                Contributors
                Panwen TIAN
                Journal
                Journal ID (nlm-ta): Zhongguo Fei Ai Za Zhi
                Journal ID (iso-abbrev): Zhongguo Fei Ai Za Zhi
                Title: Chinese Journal of Lung Cancer
                Publisher: Editorial board of Chinese Journal of Lung Cancer (No. 154 Anshan Road, Heping District, Tianjin, PRC, 300052 )
                ISSN (Print): 1009-3419
                ISSN (Electronic): 1999-6187
                Publication date (Print): 20 February 2024
                Volume: 27
                Issue: 2
                Pages: 138-146
                Affiliations
                [1] 1610041 成都，四川大学华西医院呼吸与危重症医学科，呼吸和共病全国重点实验室，精准医学四川省重点实验室（齐畅，田攀文，李为民） 1Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
                [2] 2610041 成都，四川大学华西医院呼吸健康研究所，疾病分子网络前沿科学中心，呼吸和共病研究院（李为民） 2Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
                [3] 3610041 成都，四川大学华西医院中国医学科学院创新单元（李为民） 3The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu 610041, China
                [4] 4610041 成都，四川大学华西医院肺癌中心（田攀文） 4Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu 610041, China
                Author notes
                田攀文，E-mail: mrascend@ 123456163.com
                Panwen TIAN, E-mail: mrascend@ 123456163.com
                Article
                DOI: 10.3779/j.issn.1009-3419.2024.102.06
                PMC ID: 10918244
                PubMed ID: 38453446
                SO-VID: b0b3a97e-89ad-4604-a76f-c32c6e44882d
                Copyright © 版权所有 © 2024《中国肺癌杂志》编辑部Copyright © 2024, Chinese Journal of Lung Cancer.
                License:

                This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) License. See: https://creativecommons.org/licenses/by/3.0/.

                History
                Date received : 20 December 2023
                Funding
                Funded by: 国家自然科学基金项目
                Funded by: National Natural Science Foundation of China(to Panwen TIAN)
                Award ID: 82072598
                Funded by: 国家自然科学基金项目
                Funded by: National Natural Science Foundation of China(to Weimin LI)
                Award ID: 92159302
                Funded by: 四川省科技厅重大专项
                Funded by: Science and Technology Project of Sichuan, China (to Weimin LI)
                Award ID: 2022ZDZX0018
                Funded by: 四川大学华西医院1-3-5卓越计划项目
                Funded by: 1-3-5 project for disciplines of excellence, West China Hospital, Sichuan University, China(to Panwen TIAN)
                Award ID: ZYJC21052
                Funded by: 四川大学华西医院1-3-5卓越计划项目
                Funded by: 1-3-5 project for disciplines of excellence, West China Hospital, Sichuan University, China(to Weimin LI)
                Award ID: ZYGD22009
                Categories
                Subject: Review

                Keywords: 肺肿瘤,新辅助治疗,免疫检查点抑制剂,围手术期,可切除非小细胞肺癌,lung neoplasms,neoadjuvant therapy,immune checkpoint inhibitors,perioperative period,resectable non-small cell lung cancer
                Data availability:
                Keywords: 肺肿瘤, 新辅助治疗, 免疫检查点抑制剂, 围手术期, 可切除非小细胞肺癌, lung neoplasms, neoadjuvant therapy, immune checkpoint inhibitors, perioperative period, resectable non-small cell lung cancer

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