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      Immunotherapy in non-small cell lung cancer: rationale, recent advances and future perspectives

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          Abstract

          Lung cancer, with non-small cell lung cancer (NSCLC) being the major type, is the second most common malignancy and the leading cause of cancer-related death globally. Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has been one of the greatest advances in recent years for the treatment of solid tumors including NSCLC. However, not all NSCLC patients experience an effective response to immunotherapy with the established selection criteria of programmed death ligand 1 (PD-L1) and tumor mutational burden (TMB). Furthermore, a considerable proportion of patients experience unconventional responses, including pseudoprogression or hyperprogressive disease (HPD), immune-related toxicities, and primary or acquired resistance during the immunotherapy process. To better understand the immune response in NSCLC and provide reference for clinical decision-making, we herein review the rationale and recent advances in using immunotherapy to treat NSCLC. Moreover, we discuss the current challenges and future strategies of this approach to improve its efficacy and safety in treating NSCLC.

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          Most cited references127

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

            Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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              Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

              Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.
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                Author and article information

                Contributors
                Journal
                Precis Clin Med
                Precis Clin Med
                pcm
                Precision Clinical Medicine
                Oxford University Press
                2096-5303
                2516-1571
                December 2021
                02 December 2021
                02 December 2021
                : 4
                : 4
                : 258-270
                Affiliations
                Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University , Chengdu 610041, China
                Precision Medicine Research Center, West China Hospital, Sichuan University , Chengdu 610041, China
                Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College , Chengdu 610500, China
                Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University , Chengdu 610041, China
                Department of Clinical Research Management, West China Hospital, Sichuan University , Chengdu 610041, China
                Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University , Chengdu 610041, China
                Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University , Chengdu 610041, China
                Precision Medicine Research Center, West China Hospital, Sichuan University , Chengdu 610041, China
                Author notes
                Correspondence: Weimin Li, weimin003@ 123456163.com
                Article
                pbab027
                10.1093/pcmedi/pbab027
                8982543
                35692863
                2faec09f-e6c8-4b58-9764-c6d506eb1aad
                © The Author(s) 2021. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 October 2021
                : 29 November 2021
                : 30 November 2021
                Page count
                Pages: 13
                Funding
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 81871890
                Award ID: 91859203
                Funded by: Science and Technology Support Program of Sichuan Province;
                Award ID: 2020YFS0572
                Categories
                Review
                AcademicSubjects/MED00010

                non-small cell lung cancer,immunotherapy,immune checkpoint inhibitors,adoptive cell therapy,vaccine

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