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      Functional and Therapeutic Significance of Tumor-Associated Macrophages in Colorectal Cancer

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          Abstract

          The role of the tumor microenvironment (TME) in the progression of colorectal cancer (CRC) and its acquisition of resistance to treatment become the research hotspots. As an important component of TME, the tumor-associated macrophages (TAMs) regulate multiple critical oncogenic processes, namely, occurrence, proliferation, metastasis, and drug resistance in CRC. In this review, we have discussed the functional and therapeutic significance of TAMs in CRC. M1 macrophages act as the tumor suppressor while M2 macrophages promote CRC. The polarization of TAMs is mainly regulated by the pathways such as NFKB1 pathways, STAT3 pathways, WNT5A pathways, and PI3K pathways in CRC. Furthermore, the M2 polarization of TAMs is not only controllable but also reversible. Finally, we provide insights into the TAMs-targeted therapeutic strategies.

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          Most cited references139

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          Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer

          Programmed death 1 (PD-1) blockade has clinical benefit in microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) tumors after previous therapy. The efficacy of PD-1 blockade as compared with chemotherapy as first-line therapy for MSI-H-dMMR advanced or metastatic colorectal cancer is unknown.
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            Delivery technologies for cancer immunotherapy

            Immunotherapy has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing, with numerous treatments in clinical and preclinical development. However, a key challenge in the broad implementation of immunotherapies for cancer remains the controlled modulation of the immune system, as these therapeutics have serious adverse effects including autoimmunity and nonspecific inflammation. Understanding howto increase the response rates to various classes of immunotherapy is key to improving efficacy and controlling these adverse effects. Advanced biomaterials and drug delivery systems, such as nanoparticles and the use of T cells to deliver therapies, could effectively harness immunotherapies and improve their potency while reducing toxic side effects. Here, we discuss these research advances, as well as the opportunities and challenges for integrating delivery technologies into cancer immunotherapy, and we critically analyse the outlook for these emerging areas.
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              Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors

              According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. Nearly 2 million new cases and about 1 million deaths are expected in 2018. CRC incidence has been steadily rising worldwide, especially in developing countries that are adopting the “western” way of life. Obesity, sedentary lifestyle, red meat consumption, alcohol, and tobacco are considered the driving factors behind the growth of CRC. However, recent advances in early detection screenings and treatment options have reduced CRC mortality in developed nations, even in the face of growing incidence. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Meanwhile, the general population can reduce their risk by lowering their red meat, alcohol, and tobacco consumption and raising their consumption of fibre, wholesome foods, and certain vitamins and minerals.
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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
                02 February 2022
                2022
                : 12
                : 781233
                Affiliations
                [1] 1 Department of General Surgery, Huashan Hospital, Fudan University , Shanghai, China
                [2] 2 Cancer Metastasis Institute, Fudan University , Shanghai, China
                Author notes

                Edited by: Zhanlong Shen, Peking University People’s Hospital, China

                Reviewed by: Shuji Ogino, Brigham and Women’s Hospital and Harvard Medical School, United States; Giorgio Stassi, University of Palermo, Italy

                *Correspondence: Jinhong Chen, jinhongch@ 123456hotmail.com

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Gastrointestinal Cancers: Colorectal Cancer, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.781233
                8847181
                35186730
                f140ece6-5963-4971-ba40-7d1ccf9d7f34
                Copyright © 2022 Li, Chen, Han, Ma, Zheng and Chen

                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
                : 22 September 2021
                : 10 January 2022
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 140, Pages: 13, Words: 5006
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 8200033791, 8207034966
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                colorectal cancer,tumor-associated macrophages,mechanism,tumor microenvironment,treatment

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