Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation
Open accessAbstract
Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co-inhibitory receptor expression on T cells dampens effector T cell responses. Unfortunately, many patients still fail to respond to therapies that target CTLA-4 and PD-1. The next wave of co-inhibitory receptor targets that are being explored in clinical trials include Lag-3, Tim-3, and TIGIT. These receptors, although they belong to the same class of receptors as PD-1 and CTLA-4, exhibit unique functions, especially at tissue sites where they regulate distinct aspects of immunity. Increased understanding of the specialized functions of these receptors will inform the rational application of therapies that target these receptors to the clinic.
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During chronic inflammation, T cells become exhausted and upregulate non-redundant inhibitory receptors such as PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT that limit their effectiveness.
“During chronic inflammation in particular, T cells are known to become exhausted and to upregulate a wide range of non-redundant inhibitory receptors that limit their effectiveness, such as PD-1, CTLA-4, T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), or T-Cell immunoreceptor with Ig And ITIM domains (TIGIT) [See Table 1 (9–11)].”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [11]
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References 135 · Cited by 2,096
- Authors
- Anderson, A. C., Joller, N., & Kuchroo, V. K.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Zurich (CH)
- Corresponding author
- Kuchroo, Vijay K.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 44
- Issue
- 5
- Pages
- 989-1004
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4942846
- OpenAlex
- W2403400382
- Cited by
- 2,096
- References
- 135
- Citations by year
- 2026: 136 · 2025: 213 · 2024: 231 · 2023: 273 · 2022: 268 · 2021: 278 · 2020: 257 · 2019: 181 · 2018: 157 · 2017: 77 · 2016: 22 · 2014: 1
- FWCI
- 14.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA187975)
- National Institute of Allergy and Infectious Diseases (P01AI073748, P01AI056299, P01AI039671)
- National Institute of Neurological Disorders and Stroke (P01NS076410, R01NS045937)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- LAG-3, TIM-3, TIGIT, co-inhibitory receptors, immune checkpoint blockade, T cell regulation, CTLA-4, PD-1, chronic disease, cancer immunotherapy, tissue-specific immunity
- MeSH terms
- Hepatitis A Virus Cellular Receptor 2, Lymphocyte Activation Gene 3 Protein, Animals, Humans, Immune Tolerance, Lymphocyte Activation, Receptors, Immunologic, T-Lymphocytes, Signal Transduction, Antigens, CD, Receptor Cross-Talk, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
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