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

By Joel Crespo, Haoyu Sun, T. Welling, Zhigang Tian, W. Zou. Current Opinion in Immunology, 2013

703 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/34f00be94575f3b40fcd8874451f68611018ad1c

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Citations in the corpus

Cellular Senescence: Aging, Cancer, and Injury. (2019, background): “Exhausted lymphocytes have short telomeres, cannot proliferate even in the presence of costimulatory molecules, are resistant to apoptosis, but not metabolically active, whereas senescent lymphocytes are still metabolically active and express high levels of senescence immunological markers (80, 110,”
Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer (2017, positive): “…cancer cell proliferation (Mantovani et al., 2008), the induction of tumor vascularization through paracrine mechanisms (De Palma et al., 2007), and the establishment of complex immunosuppressive networks that restrain the protective function of cancer-reactive T cells (Crespo et al., 2013).”
From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review) (2018, positive): “…APC in vivo are in fact normal ‘self’ peptides, with only a few from foreign antigens (29). ii) Lack of a costimulatory molecule of a tumor cell, expressing a tumor‑associated antigen (TAA), leads to a hyporesponsive state in a TAA‑specific responding T‑cell, which is known as T-cell anergy (30).”
The Principles of Engineering Immune Cells to Treat Cancer (2017, background): “T cell exhaustion and senescence are often used interchangeably; however, they are now considered as distinct states of differentiation (Akbar and Henson, 2011; Crespo et al., 2013).”
Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis (2016, positive): “Tumor-Specific CD8 T Cells Isolated from Pre- and EarlyMalignant Lesions Exhibit theMolecular Hallmarks of CD8 T Cells from Late-Stage Human and Mouse Tumors Because T cells from pre-malignant lesions displayed phenotypic and functional characteristics of dysfunctional T cells from latestage establi”
Type 1 diabetes (2002, neutral): “One mechanism that can lead to T cell unresponsiveness in vivo is T cell exhaustion ( 4 , 6 , 9 – 11 ).”
Metabolic competition in the tumor microenvironment is a driver of cancer progression (2015, background): “Anergy, exhaustion, and senescence, have all been described in T cells from cancer patients (Crespo et al., 2013; Wherry, 2011)—and chronic TCR stimulation, lack of costimulation, and active suppression by other cells are implicated in T cell dysfunction.”