start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=5 article-no= start-page=1086 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of Tumor-Associated Macrophages in Sarcomas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary Recent studies have shown the pro-tumoral role of tumor-associated macrophages (TAMs) not only in major types of carcinomas but also in sarcomas. Several types of TAM-targeted drugs have been investigated under clinical trials, which may represent a novel therapeutic approach for bone and soft-tissue sarcomas. Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRP alpha, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas. en-copyright= kn-copyright= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HealeyJohn en-aut-sei=Healey en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OguraKoichi en-aut-sei=Ogura en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HataToshiaki en-aut-sei=Hata en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KureMiho en-aut-sei=Kure en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center kn-affil= affil-num=3 en-affil=Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= en-keyword=sarcoma kn-keyword=sarcoma en-keyword=tumor-associated macrophage kn-keyword=tumor-associated macrophage en-keyword=prognosis kn-keyword=prognosis en-keyword=clinical trial kn-keyword=clinical trial en-keyword=immunotherapy kn-keyword=immunotherapy END