T cell exhaustion (Tex) is a state of dysfunction that results from persistent antigen and inflammation, both of which commonly occur in cancer tissue. The reversal or prevention of exhaustion is a major area of research for cancer immunotherapy. Currently, analyzing multiple phenotypic and functional parameters in combination is required for the identification of Tex populations. A better understanding of T cell exhaustion mechanisms and the identification of unique phenotypic markers for Tex cells will greatly facilitate the advancement of adoptive cell transfer strategies.
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Hallmarks of T Cell Exhaustion
Hallmarks commonly used to monitor CD4+ and CD8+ T cell exhaustion are listed below. Click the links for relevant products, including proteins (GMP-grade available!), ELISAs, flow cytometry antibodies, and assays for proliferation and cytotoxicity.
CD8+ T cells
- Co-express multiple inhibitory receptors: PD-1, CTLA-4, LAG-3, TIM-3, 2B4/CD244/SLAMF4, CD160, TIGIT
- Loss of IL-2 production, proliferative capacity, ex vivo cytolytic activity
- Impairment in the production of TNF-alpha, IFN-gamma, and cc (beta) chemokines
- Degranulation; expression of high levels of Granzyme B
- Poor responsiveness to IL-7 and IL-15, which drive memory T cell antigen-dependent proliferation long after antigen elimination
- Cell death, likely due to overstimulation
CD4+ T cells
- Co-express multiple inhibitory receptors: PD-1, CTLA-4, LAG-3, TIM-3, 2B4/CD244/SLAMF4, CD160, TIGIT
- Loss of IL-2 production, proliferative capacity, ex vivo cytolytic activity
- Impairment in the production of TNF-alpha, IFN-gamma, and cc (beta) chemokines
- Altered expression of GATA-3, Bcl-6, and Helios
- Few CD4+ Tex cells express EOMES
- Become skewed towards a T Follicular Helper (Tfh) cell phenotype
- Show earlier manifestation of dysfunction compared to CD8+ Tex cells
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Human XL Cytokine Antibody Array
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Cytokine Secretion Profile of Leukemia Cells. THP-1 human acute monocytic leukemia cells were untreated or treated with 1 µg/mL of Recombinant Human IFN-gamma (Catalog # 285-IF) for 16 hours and 1 µg/mL of LPS for 8 hours. Cell supernates were analyzed using the Human XL Cytokine Array Kit (Catalog # ARY022). |
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