T Cell Dysfunction in Cancer

By D. Thommen, Ton N. Schumacher. Cancer Cell, 2018

1,105 citations recorded by the source corpus.

Therapeutic reinvigoration of tumor-specific T cells has greatly improved clinical outcome in cancer. Nevertheless, many patients still do not achieve durable benefit. Recent evidence from studies in murine and human cancer suggest that intratumoral T cells display a broad spectrum of (dys-)functional states, shaped by the multifaceted suppressive signals that occur within the tumor microenvironment. Here we discuss the current understanding of T cell dysfunction in cancer, the value of novel technologies to dissect such dysfunction at the single cell level, and how our emerging understanding of T cell dysfunction may be utilized to develop personalized strategies to restore antitumor immunity.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/23bac04158b72ff82c2c3a52d0e558ecdf6f274d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Anderson
2. V. Kuchroo
3. Ton N. Schumacher
4. Zemin Zhang
5. C. Blank

In Oncology

1. Ton N. Schumacher
2. Zemin Zhang
3. A. Anderson
4. C. Blank
5. V. Kuchroo

Citations in the corpus

• Cytotoxic CD8+ T cells in cancer and cancer immunotherapy (2020, background): “Therapy resistance can be correlated with increased expression of VEGF,(68) which affects CD8 T-cell functionality both directly and indirectly via the suppression of dendritic cell maturation and recruitment of suppressive cell populations.(69)”
• CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review (2018, background): “This higher ratio would cause dysfunction and exhaustion of CTLs (Gangaplara et al., 2018; Martin et al., 2018; Thommen & Schumacher, 2018).”
• Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma (2018, positive): “The large number (n = 145) of CD8 metacells were initially subdivided into a transitional CD8 effector T (GZMK+) pool, a cytotoxic CD8 effector T (GZMH+) pool, and a large cluster of dysfunctional CD8 T cells, marked by high expression of immune checkpoint molecules such as PD-1 and LAG3.”
• Pan-cancer single-cell landscape of tumor-infiltrating T cells (2021, background): “In addition, multiple TME factors contribute to the exhaustion phenotype (8), and distinct regulatory processes dictating the phenotypes and abundance of T cells may exist within the TMEs of various cancer types.”
• Lag-3, Tim-3, and TIGIT co-inhibitory receptors with specialized functions in immune regulation (2016, background): “Fyn has been implicated in the induction of T cell anergy (Davidson et al., 2007) and is known to be a key kinase to activate phosphoprotein associated with glycosphingolipid microdomains (PAG), which recruits Csk to suppress Lck function (Salmond et al., 2009; Smida et al., 2007).”