High efficiency CRISPR knock-in demonstrates that TCF1 is insufficient to reverse T cell exhaustion - PubMed
4 days ago
- #Immunotherapy
- #T cell exhaustion
- #CRISPR
- CD8+ T cell exhaustion is a regulatory state caused by chronic antigen stimulation in cancer and persistent infections.
- The stem-like sub-populations of exhausted T cells are crucial for immunotherapy efficacy.
- TCF1 is necessary and sufficient for the formation and maintenance of stem-like T cell populations.
- The study investigates whether TCF1 can revert terminally exhausted T cells back to a stem-like state.
- High efficiency CRISPR knock-in was used to engineer T cells with constitutive or conditional TCF1 overexpression.
- Only constitutive TCF1 overexpression increased the stem-like T cell pool, not conditional overexpression.
- TCF1 can slow stem-like T cell differentiation but cannot revert differentiated cells back to a stem-like state.