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      The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer

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          Abstract

          The use of programmed cell-death protein 1 (PD-1)/programmed cell-death ligand 1 (PD-L1) inhibitors is the standard therapy for the first-line or second-line treatment of patients with non-small-cell lung cancer (NSCLC). In contrast to current traditional treatments such as chemotherapy or radiotherapy, anti-PD-1 and anti-PD-L1 treatments can directly attenuate tumour-mediated exhaustion and effectively modulate the host anti-tumour immune response in vivo. In addition, compared with traditional therapy, PD-1/PD-L1 inhibitor monotherapy can significantly prolong survival without obvious side effects in the treatment of advanced NSCLC. Ideally, several biomarkers could be used to monitor the safety and effectiveness of anti-PD-1 and anti-PD-L1 treatments; however, the current lack of optimal prognostic markers remains a widespread limitation and challenge for further clinical applications, as does the possibility of immune-related adverse events and drug resistance. In this review, we aimed to summarise the latest progress in anti-PD-1/anti-PD-L1 treatment of advanced NSCLC, worldwide, including in China. An exploration of underlying biomarker identification and future challenges will be discussed in this article to facilitate translational studies in cancer immunotherapy.

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          Most cited references168

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          Cancer statistics, 2020

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
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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
                Ther Adv Med Oncol
                Ther Adv Med Oncol
                TAM
                sptam
                Therapeutic Advances in Medical Oncology
                SAGE Publications (Sage UK: London, England )
                1758-8340
                1758-8359
                15 February 2021
                2021
                : 13
                : 1758835921992968
                Affiliations
                [1-1758835921992968]Department of Respiratory Disease, Thoracic Disease Centre, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
                [2-1758835921992968]Intensive Care Unit, The First People’s Hospital of Changde City, Changde, Hunan, PR China
                [3-1758835921992968]Lung Cancer and Gastroenterology Department, Hunan Cancer Hospital, Affiliated Tumour Hospital of Xiangya Medical School of Central South University, Changsha, Hunan, PR China
                [4-1758835921992968]Thoracic Medicine Department 1, Hunan Cancer Hospital, Affiliated Tumour Hospital of Xiangya Medical School of Central South University, Changsha, Hunan, PR China
                [5-1758835921992968]Ningxia Key Laboratory of Cerebrocranial Diseases, School of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, PR China
                [6-1758835921992968]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
                [7-1758835921992968]Department of Respiratory Disease, Thoracic Disease Centre, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
                Author notes
                Author information
                https://orcid.org/0000-0002-8079-4722
                https://orcid.org/0000-0001-9374-6466
                Article
                10.1177_1758835921992968
                10.1177/1758835921992968
                7890731
                33643442
                a6b2a774-c5c0-475f-859d-39bb7d328abd
                © The Author(s), 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 18 August 2020
                : 13 January 2021
                Funding
                Funded by: National Natural Science Foundation of China, FundRef https://doi.org/10.13039/501100001809;
                Award ID: 81802278, 81900563, 81670017, 81960232, and 820012
                Funded by: natural science foundation of hunan province, FundRef https://doi.org/10.13039/501100004735;
                Award ID: 2019JJ50361 and 2020JJ4418
                Categories
                Immunotherapy for Lung Cancer: Special Collection Progress, Opportunities and Challenges
                Review
                Custom metadata
                January-December 2021
                ts1

                immunotherapy,non-small cell lung cancer (nsclc),pd-1/pd-l1 inhibitors,predictive biomarkers,progress and challenges

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