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      Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring

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          Abstract

          Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.

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          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

            Summary The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies
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              Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

              Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of the tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote tumor growth, angiogenesis, invasion and metastasis, along with extracellular matrix (ECM) remodeling and even chemoresistance. Numerous previous studies have confirmed the critical role of the interaction between CAFs and tumor cells in tumorigenesis and development. However, recently, the mutual effects of CAFs and the tumor immune microenvironment (TIME) have been identified as another key factor in promoting tumor progression. The TIME mainly consists of distinct immune cell populations in tumor islets and is highly associated with the antitumor immunological state in the TME. CAFs interact with tumor-infiltrating immune cells as well as other immune components within the TIME via the secretion of various cytokines, growth factors, chemokines, exosomes and other effector molecules, consequently shaping an immunosuppressive TME that enables cancer cells to evade surveillance of the immune system. In-depth studies of CAFs and immune microenvironment interactions, particularly the complicated mechanisms connecting CAFs with immune cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding the direct and indirect crosstalk between CAFs and infiltrating immune cells and further summarize the possible immunoinhibitory mechanisms induced by CAFs in the TME. In addition, we present current related CAF-targeting immunotherapies and briefly describe some future perspectives on CAF research in the end.
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                Author and article information

                Contributors
                goldenwang2000@ntu.edu.cn
                jiang9909@hotmail.com
                mayushui@tongji.edu.cn
                fuda@shsmu.edu.cn
                Journal
                Mol Cancer
                Mol Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                20 January 2022
                20 January 2022
                2022
                : 21
                : 25
                Affiliations
                [1 ]GRID grid.440660.0, ISNI 0000 0004 1761 0083, National Engineering Research Center of Rice and Byproduct Deep Processing, College of Food Science and Engineering, , Central South University of Forestry and Technology, ; Changsha, 410004 Hunan China
                [2 ]GRID grid.260483.b, ISNI 0000 0000 9530 8833, Institute of Oncology, Affiliated Tumor Hospital of Nantong University, ; Nantong, 226631 Jiangsu China
                [3 ]GRID grid.412532.3, Department of Pathology, , Shanghai Pulmonary Hospital, Tongji University School of Medicine, ; Shanghai, 200433 China
                [4 ]GRID grid.412538.9, ISNI 0000 0004 0527 0050, Department of Nuclear Medicine, , Shanghai Tenth People’s Hospital, Tongji University School of Medicine, ; Shanghai, 200072 China
                [5 ]GRID grid.260483.b, ISNI 0000 0000 9530 8833, Department of Immunology, , School of Medicine, Nantong University, ; Nantong, 226019 Jiangsu China
                [6 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, General Surgery, , Ruijin Hospital & Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, ; Shanghai, 200025 China
                [7 ]GRID grid.260483.b, ISNI 0000 0000 9530 8833, Department of Thoracic Surgery, , Affiliated Tumor Hospital of Nantong University, ; Nantong, 226631 Jiangsu China
                [8 ]GRID grid.260483.b, ISNI 0000 0000 9530 8833, Department of Radiotherapy, , Affiliated Tumor Hospital of Nantong University, ; Nantong, 226631 Jiangsu China
                [9 ]GRID grid.411525.6, ISNI 0000 0004 0369 1599, Department of Thoracic Surgery, , Navy Military Medical University Affiliated Changhai Hospital, ; Shanghai, 200433 China
                Author information
                http://orcid.org/0000-0002-0878-2575
                Article
                1505
                10.1186/s12943-022-01505-z
                8772097
                35057806
                2e9e2ff2-c671-494a-bcc3-2c0543a0bec4
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 2 December 2021
                : 10 January 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81472202, 81772932, 81972214, 81302065, 82071956, and 81702243
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Oncology & Radiotherapy
                lung cancer,diagnostics,liquid biopsy,ctcs,ctdna,exosomes
                Oncology & Radiotherapy
                lung cancer, diagnostics, liquid biopsy, ctcs, ctdna, exosomes

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