| First Author | Baxter AE | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 6 | Pages | 1320-1340.e10 |
| PubMed ID | 37315535 | Mgi Jnum | J:354841 |
| Mgi Id | MGI:7495417 | Doi | 10.1016/j.immuni.2023.05.008 |
| Citation | Baxter AE, et al. (2023) The SWI/SNF chromatin remodeling complexes BAF and PBAF differentially regulate epigenetic transitions in exhausted CD8(+) T cells. Immunity 56(6):1320-1340.e10 |
| abstractText | CD8(+) T cell exhaustion (Tex) limits disease control during chronic viral infections and cancer. Here, we investigated the epigenetic factors mediating major chromatin-remodeling events in Tex-cell development. A protein-domain-focused in vivo CRISPR screen identified distinct functions for two versions of the SWI/SNF chromatin-remodeling complex in Tex-cell differentiation. Depletion of the canonical SWI/SNF form, BAF, impaired initial CD8(+) T cell responses in acute and chronic infection. In contrast, disruption of PBAF enhanced Tex-cell proliferation and survival. Mechanistically, PBAF regulated the epigenetic and transcriptional transition from TCF-1(+) progenitor Tex cells to more differentiated TCF-1(-) Tex subsets. Whereas PBAF acted to preserve Tex progenitor biology, BAF was required to generate effector-like Tex cells, suggesting that the balance of these factors coordinates Tex-cell subset differentiation. Targeting PBAF improved tumor control both alone and in combination with anti-PD-L1 immunotherapy. Thus, PBAF may present a therapeutic target in cancer immunotherapy. |
