TY - JOUR
T1 - Molecular Markers of Regulatory T Cells in Cancer Immunotherapy with Special Focus on Acute Myeloid Leukemia (AML) - A Systematic Review
AU - Kaboli, Parham Jabbarzadeh
AU - Zhang, Lingling
AU - Xiang, Shixin
AU - Shen, Jing
AU - Li, Mingxing
AU - Zhao, Yueshui
AU - Wu, Xu
AU - Zhao, Qijie
AU - Zhang, Hanyu
AU - Lin, Ling
AU - Yin, Jianhua
AU - Wu, Yuanlin
AU - Wan, Lin
AU - Yi, Tao
AU - Li, Xiang
AU - Cho, Chi Hin
AU - Li, Jing
AU - Xiao, Zhangang
AU - Wen, Qinglian
N1 - Funding Information:
This research was supported by National Natural Science Foundation of China (Grant nos. 81503093, 81602166, and 81672444) and by Joint Funds of Southwest Medical University & Luzhou (2016LZX-NYD-T01, 2017LZXNYD-Z05 and 2017LZXNYD-J09).
Publisher copyright:
© 2020 Bentham Science Publishers.
PY - 2020/8
Y1 - 2020/8
N2 - The next-generation immunotherapy can only be effective if researchers have an in-depth understanding of the function and regulation of Treg cells in antitumor immunity combined with the discovery of new immunity targets. This can enhance clinical efficacy of future and novel therapies and reduces any adverse reactions arising from the latter. This review discusses tumor treatment strategies using regulatory T (Treg) cell therapy in a Tumor Microenvironment (TME). It also discusses factors affecting TME instability as well as relevant treatments to prevent future immune disorders. It is prognosticated that PD-1 inhibitors are risky and their adverse effects should be taken into account when they are administered to treat Acute Myeloid Leukemia (AML), lung adenocarcinoma, and prostate adenocarcinoma. In contrast, Treg molecular markers FoxP3 and CD25 analyzed here have stronger expression in almost all kinds of cancers compared with normal people. However, CD25 inhibitors are more effective compared to FoxP3 inhibitors, especially in combination with TGF-β blockade, in predicting patient survival. According to the data obtained from the Cancer Genome Atlas, we then concentrate on AML immunotherapy and discuss different therapeutic strategies including anti-CD25/IL-2, anti-CTLA-4, anti-IDO, anti-tyrosine kinase receptor, and anti-PI3K therapies and highlight the recent advances and clinical achievements in AML immunotherapy. In order to prognosticate the risk and adverse effects of key target inhibitors (namely against CTLA-4, FoxP3, CD25, and PD-1), we finally analyzed and compared the Cancer Genome Atlas derived from ten common cancers. This review shows that Treg cells are strongly increased in AML and the comparative review of key markers shows that Treg-based immunotherapy is not effective for all kinds of cancer. Therefore, blocking CD25(+)FoxP3(+) Treg cells is suggested in AML more than other kinds of cancer; meanwhile, Treg markers studied in other cancers have also great lessons for AML immunotherapy.
AB - The next-generation immunotherapy can only be effective if researchers have an in-depth understanding of the function and regulation of Treg cells in antitumor immunity combined with the discovery of new immunity targets. This can enhance clinical efficacy of future and novel therapies and reduces any adverse reactions arising from the latter. This review discusses tumor treatment strategies using regulatory T (Treg) cell therapy in a Tumor Microenvironment (TME). It also discusses factors affecting TME instability as well as relevant treatments to prevent future immune disorders. It is prognosticated that PD-1 inhibitors are risky and their adverse effects should be taken into account when they are administered to treat Acute Myeloid Leukemia (AML), lung adenocarcinoma, and prostate adenocarcinoma. In contrast, Treg molecular markers FoxP3 and CD25 analyzed here have stronger expression in almost all kinds of cancers compared with normal people. However, CD25 inhibitors are more effective compared to FoxP3 inhibitors, especially in combination with TGF-β blockade, in predicting patient survival. According to the data obtained from the Cancer Genome Atlas, we then concentrate on AML immunotherapy and discuss different therapeutic strategies including anti-CD25/IL-2, anti-CTLA-4, anti-IDO, anti-tyrosine kinase receptor, and anti-PI3K therapies and highlight the recent advances and clinical achievements in AML immunotherapy. In order to prognosticate the risk and adverse effects of key target inhibitors (namely against CTLA-4, FoxP3, CD25, and PD-1), we finally analyzed and compared the Cancer Genome Atlas derived from ten common cancers. This review shows that Treg cells are strongly increased in AML and the comparative review of key markers shows that Treg-based immunotherapy is not effective for all kinds of cancer. Therefore, blocking CD25(+)FoxP3(+) Treg cells is suggested in AML more than other kinds of cancer; meanwhile, Treg markers studied in other cancers have also great lessons for AML immunotherapy.
KW - Cancer immunotherapy
KW - CD25
KW - CTLA-4
KW - FoxP3
KW - PD-1
KW - Regulatory T cells
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85074896706&partnerID=8YFLogxK
U2 - 10.2174/0929867326666191004164041
DO - 10.2174/0929867326666191004164041
M3 - Review article
C2 - 31584362
AN - SCOPUS:85074896706
SN - 0929-8673
VL - 27
SP - 4673
EP - 4698
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 28
ER -
