Exhausted CD8 T cells (TEX) are a distinct state of T cell differentiation associated with failure to clear chronic viruses and cancer. Immunotherapies such as PD-1 blockade can reinvigorate TEX cells, but reinvigoration is not durable. A major unanswere
Exhausted T cells (TEX) are a hallmark of cancer and chronic viral infection, reflecting failure to clear tumors and viruses. Checkpoint blockade revolutionized immunotherapy by reinvigorating TEX, however, not all cancer patients benefit from immunotherapy and responses are not durable. Thus, deeper ...
Our study focused on exhaust CD8 + T cells (CD8 + Tex). The recent surge in cancer immunotherapy, primarily based on checkpoint blockade, has been a breakthrough in treating various cancer types. However, certain factors are hindering the progress of these treatments, such as varying ...
Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from...
TCF-1 mediated a T-bet-to-Eomes transcription factor transition in Tex precursors by promoting Eomes expression and drove c-Myb expression that controlled Bcl-2 and survival. These data define a role for TCF-1 in early-fate-bifurcation-driving Tex precursor cells and also identify PD-1 as a...
T cell-intrinsic, TCR-independent CD137 signaling stimulated the proliferation and the terminal differentiation of Tex precursor cells through a mechanism involving the RelA and cRel canonical NF-κB subunits and Tox-dependent chromatin remodeling. While Tex cell accumulation induced by prophylactic CD137...
Cytotoxic CD8+ T cells (CTL) encountering chronic antigen and metabolic restriction can differentiate to a terminally exhausted state (Texh), marked by hyporesponsiveness and metabolic, epigenetic, and transcriptional dysfunction. 4–8 While enrichment of this population in tumor is a negative ...
3. Although Tex cells lose proliferative capacity and undergo apoptosis during terminal differentiation, they are steadily replenished by a distinct multipotent population, termed precursors (or progenitors) of exhausted T (Tpex) cells3,4,5,6,7. Tpex cells can be identified by the expression of...
Thus, a terminal Tex subset could be used as a proxy for a tumor-reactive T-cell compartment31,33. To further support this notion, we analyzed previously reported signature genes of tumor antigen-specific T cells30,31—ENTPD1 and ITGAE—and found that they were specifically expressed in ...
These Texeff autoimmune cells may still drive β cell killing, differing from dysfunctional, fully exhausted CD8+ T cells observed in chronic viral infection and cancer.52,53,84,85,86,87,88,89,90,91,92 Furthermore, we identified an oxidative stress-related signature in intra-islet Texint ...