T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment

Highlights ► We provide an updated view on effector T cell compartment in the tumor microenvironment. ► We describe dysfunctional T cell subsets in the tumor microenvironment. ► We discuss co-inhibitory and co-stimulatory molecular networks in the tumor microenvironment. ► We review stem like-memory...

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Published in	Current opinion in immunology Vol. 25; no. 2; pp. 214 - 221
Main Authors	Crespo, Joel, Sun, Haoyu, Welling, Theodore H, Tian, Zhigang, Zou, Weiping
Format	Journal Article
Language	English
Published	England Elsevier Ltd 01.04.2013
Subjects	Allergy and Immunology Animals Cellular Senescence Clonal Anergy - immunology Humans Neoplasms - immunology Neoplasms - therapy Stem Cells - immunology T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes - pathology Tumor Microenvironment - immunology
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Abstract	Highlights ► We provide an updated view on effector T cell compartment in the tumor microenvironment. ► We describe dysfunctional T cell subsets in the tumor microenvironment. ► We discuss co-inhibitory and co-stimulatory molecular networks in the tumor microenvironment. ► We review stem like-memory T cell subsets (e.g. Th17) in the tumor microenvironment. ► We suggest anti-cancer modality by targeting T cell dysfunction and stemness.
AbstractList	Human tumors progress despite the presence of tumor associated antigen (TAA)-specific T cells. Many different molecular and cellular mechanisms contribute to the failure of T cells to eradicate the tumor. These include immune suppressive networks that impair ongoing T cell function and enable tumor escape. Recent studies have started to reveal the nature of effector T cells in the tumor microenvironment. In this article we discuss T cell anergy, exhaustion, senescence and stemness, and review the phenotype of dysfunctional T cell subsets and the underlying molecular mechanisms in the tumor microenvironments. We suggest that targeting T cell dysfunctional mechanisms and introducing/promoting T cell stemness are important approaches to treat patients with cancer. ► We provide an updated view on effector T cell compartment in the tumor microenvironment. ► We describe dysfunctional T cell subsets in the tumor microenvironment. ► We discuss co-inhibitory and co-stimulatory molecular networks in the tumor microenvironment. ► We review stem like-memory T cell subsets (e.g. Th17) in the tumor microenvironment. ► We suggest anti-cancer modality by targeting T cell dysfunction and stemness. Human tumors progress despite the presence of tumor associated antigen (TAA)-specific T cells. Many different molecular and cellular mechanisms contribute to the failure of T cells to eradicate the tumor. These include immune suppressive networks that impair ongoing T cell function and enable tumor escape. Recent studies have started to reveal the nature of effector T cells in the tumor microenvironment. In this article we discuss T cell anergy, exhaustion, senescence, and stemness, and review the phenotype of dysfunctional T cell subsets and the underlying molecular mechanisms in the tumor microenvironments. We suggest that targeting T cell dysfunctional mechanisms and introducing/promoting T cell stemness are important approaches to treat patients with cancer. Highlights ► We provide an updated view on effector T cell compartment in the tumor microenvironment. ► We describe dysfunctional T cell subsets in the tumor microenvironment. ► We discuss co-inhibitory and co-stimulatory molecular networks in the tumor microenvironment. ► We review stem like-memory T cell subsets (e.g. Th17) in the tumor microenvironment. ► We suggest anti-cancer modality by targeting T cell dysfunction and stemness.
Author	Tian, Zhigang Zou, Weiping Sun, Haoyu Crespo, Joel Welling, Theodore H
AuthorAffiliation	1 Department of Surgery, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 4 Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China 3 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 2 Graduate Program in Immunology and Tumor Biology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI
AuthorAffiliation_xml	– name: 3 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI – name: 4 Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China – name: 1 Department of Surgery, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI – name: 2 Graduate Program in Immunology and Tumor Biology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI
Author_xml	– sequence: 1 fullname: Crespo, Joel – sequence: 2 fullname: Sun, Haoyu – sequence: 3 fullname: Welling, Theodore H – sequence: 4 fullname: Tian, Zhigang – sequence: 5 fullname: Zou, Weiping
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23298609$$D View this record in MEDLINE/PubMed
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Snippet	Highlights ► We provide an updated view on effector T cell compartment in the tumor microenvironment. ► We describe dysfunctional T cell subsets in the tumor... ► We provide an updated view on effector T cell compartment in the tumor microenvironment. ► We describe dysfunctional T cell subsets in the tumor... Human tumors progress despite the presence of tumor associated antigen (TAA)-specific T cells. Many different molecular and cellular mechanisms contribute to...
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SubjectTerms	Allergy and Immunology Animals Cellular Senescence Clonal Anergy - immunology Humans Neoplasms - immunology Neoplasms - therapy Stem Cells - immunology T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes - pathology Tumor Microenvironment - immunology
Title	T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
URI	https://www.clinicalkey.es/playcontent/1-s2.0-S0952791512001938 https://dx.doi.org/10.1016/j.coi.2012.12.003 https://www.ncbi.nlm.nih.gov/pubmed/23298609 https://search.proquest.com/docview/1349093355 https://pubmed.ncbi.nlm.nih.gov/PMC3636159
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