Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancerBREAST cancerT cellsHISTONE deacetylaseIMMUNOTHERAPYESTROGEN receptorsResponses to immunotherapy are uncommon in estrogen receptor (ER)-positive breast cancer and to date, lack predictive markers. This randomized phase II ...
UMAP embedding of cell similarity. Cells are coloured by infection type.b, Signatures for naive, exhausted, precursor exhausted (Tex) and terminally exhausted cells derived from bulk ATAC-seq data are used to compute signature scores for
1a). Before transfer, the PMEL T cells showed an explicitly type 1 signature (Extended Data Fig. 1f). We found that combining type 1-centric ACT therapy and Fc–IL-4 markedly promoted CD45.2+ immune cell infiltration into the TME compared to ACT alone (Extended Data Fig. 1g). Among ...
This metabolic switch increased citrate-dependent histone acetylation, mediated by histone acetyltransferase KAT2A-ACLY interactions, at TEX signature-genes while reducing acetate-dependent histone acetylation, dependent on p300-ACSS2 complexes, at effector and memory T cell genes. Nuclear ACSS2 ...
stimulation in vitro (Supplementary Fig. 6d). Transcriptional profiling of control or Ptpn2-deleted CD8+ T cells revealed that Ptpn2-deleted CD8+ T cells were significantly enriched for the tumor infiltrating lymphocytes (TIL) Tim-3+ signature, whereas control cells were enriched for the TIL ...
Specific categories like “Secreted Signaling”, “ECM-Receptor”, and “Cell-Cell Contact” within the Cellchat database underwent examination, applying a minimum cell count criterion of 3. Markers for the “hallmark_glycolysis” pathway were obtained from the Molecular Signature Database (MSigDB)....
Despite high T cell infiltration, increased CD8+ T cells are not associated with response to programmed cell death 1 (PD-1) blockade.1 Through single-cell transcriptomic analysis, we previously identified a population of SLAMF7+ CD8+ exhausted T cells that was associated with resistance to ...
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
Mol. Cell 81, 2477–2493.e10 (2021). Article CAS PubMed PubMed Central Google Scholar Hudson, W. H. et al. Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1+ stem-like CD8+ T cells during chronic infection. Immunity 51, 1043–1058.e4 (...
CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus...