title: Interplay between Immune Checkpoint Proteins and Cellular Metabolism.
abstract: With the recent successes in immuno-oncology, renewed interest in the role of immune checkpoint modulators, such as the B7 family proteins, has escalated. The immune checkpoint proteins play a crucial role in the regulation of cellular immunity; however, their contribution to other aspects of cancer biology remains unclear. Accumulating evidence indicate that immune checkpoint proteins can regulate metabolic energetics of the tumor, the tumor microenvironment, and the tumor-specific immune response, leading to metabolic reprogramming of both malignant cells and immune cells involved in mounting and sustaining this response. Immune cell metabolism impacts the activation status of immune cells and ultimately the immune response in cancer. Tumor cells may deplete nutrients that immune cells require for optimal generation, expansion, and function. They may also generate toxic metabolites in the microenvironment or induce conserved inhibitory pathways that impair immune function and thus inhibit antitumor responses. In this review, we will discuss how cancer cells with altered expression of immune checkpoint proteins can potently inhibit immune function through the alteration of cellular and microenvironmental metabolism, providing a new perspective on the interplay between these pathways and offering a potential therapeutic intervention strategy in the treatment of malignant disease.Cancer Res; 77(6); 1245-9. ©2017 AACR.
authors.affiliation: Center for Cell Death and Metabolism, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama.
authors.forename: Sangbin
authors.initials: S
authors.lastname: Lim
authors.affiliation: Center for Cell Death and Metabolism, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Phillips
authors.affiliation: Center for Cell Death and Metabolism, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama.
authors.forename: Luciana
authors.initials: L
authors.lastname: Madeira da Silva
authors.affiliation: The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Oystein
authors.initials: O
authors.lastname: Fodstad
authors.affiliation: Center for Cell Death and Metabolism, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama. mtan@health.southalabama.edu lowen@health.southalabama.edu.
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Owen
authors.affiliation: Center for Cell Death and Metabolism, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama. mtan@health.southalabama.edu lowen@health.southalabama.edu.
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*