TY - JOUR
T1 - Role of tumor-associated macrophages in sarcomas
AU - Fujiwara, Tomohiro
AU - Healey, John
AU - Ogura, Koichi
AU - Yoshida, Aki
AU - Kondo, Hiroya
AU - Hata, Toshiaki
AU - Kure, Miho
AU - Tazawa, Hiroshi
AU - Nakata, Eiji
AU - Kunisada, Toshiyuki
AU - Fujiwara, Toshiyoshi
AU - Ozaki, Toshifumi
N1 - Funding Information:
This study was supported by a grant-in-aid for overseas research fellowships from the Yasuda Medical Foundation (2018; T.F. (Tomohiro Fujiwara)), JSPS KAKENHI Grant Number 19H03784, and a grant-in-aid for overseas research fellowships from the Japan Society for the Pro-motion of Science (201860336; T.F. (Tomohiro Fujiwara)).
Funding Information:
Funding: This study was supported by a grant-in-aid for overseas research fellowships from the Yasuda Medical Foundation (2018; T.F. (Tomohiro Fujiwara)), JSPS KAKENHI Grant Number 19H03784, and a grant-in-aid for overseas research fellowships from the Japan Society for the Promotion of Science (201860336; T.F. (Tomohiro Fujiwara))
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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 or-chestrators 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/SIRPα, 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.
AB - 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 or-chestrators 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/SIRPα, 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.
KW - Clinical trial
KW - Immunotherapy
KW - Prognosis
KW - Sarcoma
KW - Tumor-associated macrophage
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U2 - 10.3390/cancers13051086
DO - 10.3390/cancers13051086
M3 - Article
AN - SCOPUS:85101831756
VL - 13
SP - 1
EP - 17
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 5
M1 - 1086
ER -