Metabolic Interventions in Tumor Immunity: Focus on Dual Pathway Inhibitors

Author:

Chen Min1ORCID,Lan Huanrong2,Yao Shiya3,Jin Ketao3ORCID,Chen Yun4

Affiliation:

1. Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China

2. Department of Surgical Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China

3. Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China

4. Department of Colorectal Surgery, Xinchang People’s Hospital, Affiliated Xinchang Hospital, Wenzhou Medical University, Xinchang 312500, China

Abstract

The metabolism of tumors and immune cells in the tumor microenvironment (TME) can affect the fate of cancer and immune responses. Metabolic reprogramming can occur following the activation of metabolic-related signaling pathways, such as phosphoinositide 3-kinases (PI3Ks) and the mammalian target of rapamycin (mTOR). Moreover, various tumor-derived immunosuppressive metabolites following metabolic reprogramming also affect antitumor immune responses. Evidence shows that intervention in the metabolic pathways of tumors or immune cells can be an attractive and novel treatment option for cancer. For instance, administrating inhibitors of various signaling pathways, such as phosphoinositide 3-kinases (PI3Ks), can improve T cell-mediated antitumor immune responses. However, dual pathway inhibitors can significantly suppress tumor growth more than they inhibit each pathway separately. This review discusses the latest metabolic interventions by dual pathway inhibitors as well as the advantages and disadvantages of this therapeutic approach.

Funder

Zhejiang Provincial Science and Technology Projects

National Natural Science Foundation of China

Jinhua Municipal Science and Technology Projects

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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