Unknown

Dataset Information

0

Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.

ABSTRACT: Blocking Programmed Death-1 (PD-1) can reinvigorate exhausted CD8 T cells (TEX) and improve control of chronic infections and cancer. However, whether blocking PD-1 can reprogram TEX into durable memory T cells (TMEM) is unclear. We found that reinvigoration of TEX in mice by PD-L1 blockade caused minimal memory development. After blockade, reinvigorated TEX became reexhausted if antigen concentration remained high and failed to become TMEM upon antigen clearance. TEX acquired an epigenetic profile distinct from that of effector T cells (TEFF) and TMEM cells that was minimally remodeled after PD-L1 blockade. This finding suggests that TEX are a distinct lineage of CD8 T cells. Nevertheless, PD-1 pathway blockade resulted in transcriptional rewiring and reengagement of effector circuitry in the TEX epigenetic landscape. These data indicate that epigenetic fate inflexibility may limit current immunotherapies.

SUBMITTER: Pauken KE 

PROVIDER: S-EPMC5484795 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Blocking Programmed Death-1 (PD-1) can reinvigorate exhausted CD8 T cells (T<sub>EX</sub>) and improve control of chronic infections and cancer. However, whether blocking PD-1 can reprogram T<sub>EX</sub> into durable memory T cells (T<sub>MEM</sub>) is unclear. We found that reinvigoration of T<sub>EX</sub> in mice by PD-L1 blockade caused minimal memory development. After blockade, reinvigorated T<sub>EX</sub> became reexhausted if antigen concentration remained high and failed to become T<sub  ...[more]

Similar Datasets

Genomics Epigenetic inflexibility of exhausted T cells limits durability of reinvigoration by PD-1 blockade
2016-10-31 | GSE86797 | GEO
Unknown Epitherapy and immune checkpoint blockade: using epigenetic reinvigoration of exhausted and dysfunctional T cells to reimburse immunotherapy response.
| S-EPMC7175524 | biostudies-literature
Unknown Reinvigorating Exhausted T Cells by Blockade of the PD-1 Pathway.
| S-EPMC5341794 | biostudies-literature
Unknown PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1hiCD39+ CD4 T cells.
| S-EPMC7934837 | biostudies-literature
Unknown PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells.
| S-EPMC3668811 | biostudies-literature
Unknown 4-1BB co-stimulation further enhances anti-PD-1-mediated reinvigoration of exhausted CD39<sup>+</sup> CD8 T cells from primary and metastatic sites of epithelial ovarian cancers.
| S-EPMC7745695 | biostudies-literature
Unknown CD4 T Cell Depletion Substantially Augments the Rescue Potential of PD-L1 Blockade for Deeply Exhausted CD8 T Cells.
| S-EPMC4505958 | biostudies-literature
Unknown OX40- and CD27-mediated costimulation synergizes with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence.
| S-EPMC4272895 | biostudies-literature
Unknown PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis.
| S-EPMC7985249 | biostudies-literature
Transcriptomics Gene expression comparison of exhausted CD8 T cells after PD-L1 blockade alone or PD-L1 blockade combined with LPS
2018-12-01 | GSE123153 | GEO