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Molecular mechanisms of T cell co-stimulation and co-inhibition
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Co-stimulatory and co-inhibitory receptors have a pivotal role in T cell biology, as they determine the functional outcome of T cell receptor (TCR) signalling. The classic definition of T cell co-stimulation continues to evolve through the identification of new co-stimulatory and co-inhibitory receptors, the biochemical characterization of their downstream signalling events and the delineation of their immunological functions. Notably, it has been recently appreciated that co-stimulatory and co-inhibitory receptors display great diversity in expression, structure and function, and that their functions are largely context dependent. Here, we focus on some of these emerging concepts and review the mechanisms through which T cell activation, differentiation and function is controlled by co-stimulatory and co-inhibitory receptors.
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“Several genes, including C10orf54 (VISTA), LGALS9, and TNFRSF14, known to inhibit T cells (Benci et al., 2019, Chen and Flies, 2013) were broadly expressed.”
From Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020) · cites this paper as Chen and Flies, 2013
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“Notably, CD80 is also a binding partner of PD-L1 and competes with PD-1 for engaging PD-L1 (Butte et al., 2008; Park et al., 2010; Chen and Flies, 2013).”
Background
Metadata
- Authors
- Chen, L., & Flies, D. B.
- Affiliations
- Yale Cancer Center (US)
- University of New Mexico (US)
- Corresponding author
- Chen, Lieping
- Venue
- Nature Reviews Immunology
- Published
- 2013-03-08
- Volume
- 13
- Issue
- 4
- Pages
- 227-242
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC3786574
- OpenAlex
- W2130473166
- Cited by
- 3,114
- References
- 135
- Citations by year
- 2026: 148 · 2025: 258 · 2024: 259 · 2023: 276 · 2022: 305 · 2021: 312 · 2020: 310 · 2019: 250 · 2018: 275 · 2017: 238 · 2016: 195 · 2015: 148 · 2014: 101 · 2013: 35
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-06-05)
- Open access
- green
- europepmc.org
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Melanoma Research Alliance
- National Cancer Institute (CA 97085, CA 16359, CA121974, CA86721, R01CA097085, CA142779, R01CA085721, R01CA142779, P50CA121974, P30CA016359)
- National Institute of Allergy and Infectious Diseases (T32AI089704, R01AI072592, AI72592, T32AI007247)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- T cell costimulation, T cell co-inhibition, costimulatory receptors, co-inhibitory receptors, T cell receptor signaling, T cell activation, T cell differentiation, immune checkpoint molecules
- MeSH terms
- Humans, Lymphocyte Activation, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction, CD28 Antigens, B7-1 Antigen, Models, Immunological, B7-2 Antigen, Receptors, Tumor Necrosis Factor, Member 14
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