Adoptive Cell Transfer: Monitor T Cell Exhaustion
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
Discover Novel Markers for T Cell Exhaustion
Proteome Profiler™ Antibody Arrays allow you to measure the expression levels of up to 111 cytokines simultaneously using only standard Western blotting equipment. If you want more flexibility, build your own panel of up to 100 analytes with Luminex® Screening Assays.
Human XL Cytokine Antibody Array
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).
Luminex® Screening Assays
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