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      Progress on neoadjuvant immunotherapy in resectable non-small cell lung cancer and potential biomarkers

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          Abstract

          Immune checkpoint inhibitors (ICIs) are highly concerned in the treatment of non-small cell lung cancer (NSCLC), represented by inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), and inhibitors of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). The introduction of immunotherapy in the treatment of perioperative NSCLC has improved the prognosis to a great extent, as demonstrated by several phase II and III clinical trials. The target population for immunotherapy in early-stage NSCLC is still under discussion, and the biomarkers for neoadjuvant immunotherapy population selection are the next pending problem. The predictive efficacy of many potential makers is still being explored, including PD-L1 expression levels, tumor mutation burden, circulating tumor DNA, components of the tumor microenvironment, and several clinical factors. We summarize key findings on the utility of ICIs in clinical trials of preoperative NSCLC patients and conclude analyses of relevant biomarkers to provide a better understanding of potentially predictive biomarkers in neoadjuvant immunotherapy.

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          Most cited references80

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          Microenvironmental regulation of tumor progression and metastasis.

          Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
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            Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

            There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers.
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              Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study

              Tumour mutational burden (TMB) has been retrospectively correlated with response to immune checkpoint blockade. We prospectively explored the association of high tissue TMB (tTMB-high) with outcomes in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                24 January 2023
                2022
                : 12
                : 1099304
                Affiliations
                [1] 1 CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences Peking Union Medical College , Beijing, China
                [2] 2 Department of Thoracic Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University , Taiyuan, China
                [3] 3 Department of Medical Oncology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University , Taiyuan, China
                Author notes

                Edited by: Fan Yang, Peking University People’s Hospital, China

                Reviewed by: Shixiang Wang, Sun Yat-sen University Cancer Center (SYSUCC), China; Gabriele Madonna, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Italy

                *Correspondence: Jianchun Duan, duanjianchun79@ 123456163.com

                This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.1099304
                9902866
                36761426
                02c85a93-bf36-4467-b06e-f26aaf592d7d
                Copyright © 2023 Wu, Chau, Bai, Zhuang, Wang and Duan

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 November 2022
                : 31 December 2022
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 80, Pages: 12, Words: 6611
                Funding
                This work was supported by the General Program of National Natural Science Foundation of China (81972905).
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                non-small cell lung cancer,neoadjuvant therapy,immune checkpoint inhibitors,pd-l1,circulating tumor dna,tumor mutation burden

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