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HLA-I evolutionary divergence confers response to PD-1 blockade plus chemotherapy in untreated advanced non-small-cell lung cancer

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机构： [1]Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China [2]State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China [3]School of Life Science and Technology, Shanghai- Tech University, Shanghai, China [4]University of Chinese Academy of Sciences, Beijing, China [5]Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China [6]First Ward of Respiratory Medicine, Harbin Medical University Cancer Hospital, Harbin, China [7]Department of Thoracic Surgery, Yunnan Cancer Hospital and the Third Affiliated Hospital of Kunming Medical University and Yunnan Cancer Center, Kunming, China [8]Department of Medical Oncology-Chest (1), Hunan Cancer Hospital, Changsha, China [9]Department of Medical Oncology, Jilin Cancer Hospital, Changchun, China [10]Department of Oncology, Henan Cancer Hospital, Zhengzhou, China [11]Department of Chemotherapy Oncology, Anhui Provincial Hospital, Hefei, China [12]Respiratory Medicine, The First Affiliated Hospital of Zhejiang University, Hangzhou, China [13]Internal Medicine Ward 2, Linyi Cancer Hospital, Linyi, China [14]Respiratory Department, The Northern Jiangsu People’s Hospital, Yangzhou, China [15]Oncology Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China [16]Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China [17]Department of Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China [18]Department of Medical Oncology, The First Hospital of China, Medical University, Shenyang, China [19]Department of Medical Oncology, Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, China [20]Department of Thoracic Medical Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China [21]Department of Respiratory, Shandong Cancer Hospital and Institute, Jinan, China [22]Department of Thoracic Oncology, Hubei Cancer Hospital, Wuhan, China [23]The Second Department of Thoracic Oncology, Beijing Cancer Hospital, Beijing, China [24]Department of Oncology, Jiangsu Province Hospital, Nanjing, China [25]Department of Medical Oncology, The First Bethune Hospital of Jilin University, Changchun, China [26]Oncology Department, General Hospital of Chinese People’s Liberation Army, Beijing, China [27]Department of Thoracic Oncology, Sichuan Provincial Cancer Hospital, Chengdu, China [28]Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China [29]Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China [30]Department of Medical Oncology, Anhui Chest Hospital, Hefei, China [31]Department of Thoracic Medical Oncology, West China Hospital, Sichuan University, Chengdu, China [32]Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals, China [33]Department of Pulmonary and Critical Care Medicine, Zhangjiagang Hospital of Traditional Chinese Medicine, Suzhou, China [34]Genecast Biotechnology Co., Ltd, Jiangsu Province,China [35]Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China,School of Oncology, Capital Medical University, Beijing, China [36]Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.

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PD-1 blockade plus chemotherapy has become the new standard of care in patients with untreated advanced non-small-cell lung cancer (NSCLC), whereas predictive biomarkers remain undetermined.We integrated clinical, genomic and survival data of 427 NSCLC patients treated with first-line PD-1 blockade plus chemotherapy or chemotherapy from two phase 3 trials (CameL and CameL-sq) and investigated the predictive and prognostic value of HLA class I evolutionary divergence (HED).High HED could predict significantly improved objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in those received PD-1 blockade plus chemotherapy (In the CameL trial, ORR: 81.8% vs. 53.2%; P = 0.032; PFS: hazard ratio [HR], 0.47; P = 0.012; OS: HR, 0.40; P = 0.014; In the CameL-sq trial, ORR: 89.2% vs 62.3%; P = 0.007; PFS: HR, 0.49; P = 0.005; OS: HR, 0.38; P = 0.002), but not chemotherapy. In multivariate analysis adjusted for PD-L1 expression and tumor mutation burden, high HED was independently associated with markedly better ORR, PFS and OS in both two trials. Moreover, joint utility of HED and PD-L1 expression showed better performance than either alone in predicting treatment benefit from PD-1 blockade plus chemotherapy. Single-cell RNA sequencing of 58,977 cells collected from 11 patients revealed that tumors with high HED had improved antigen presentation and T cell mediated antitumor immunity, indicating an inflamed tumor microenvironment phenotype.These findings suggest that high HED could portend survival benefit in advanced NSCLC treated with first-line PD-1 blockade plus chemotherapy.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 1 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区肿瘤学

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出版当年[2023]版：

Q1 ONCOLOGY

最新[2023]版：

Q1 ONCOLOGY

影响因子： 10 最新[2023版] 11.1 最新五年平均 10 出版当年[2023版] 11.1 出版当年五年平均 11.5 出版前一年[2022版]

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第一作者机构： [1]Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China

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通讯作者：

通讯机构： [1]Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China [2]State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China [3]School of Life Science and Technology, Shanghai- Tech University, Shanghai, China [4]University of Chinese Academy of Sciences, Beijing, China [36]Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.

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