| First Author | Le PT | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 738958 | PubMed ID | 34721405 |
| Mgi Jnum | J:312719 | Mgi Id | MGI:6785574 |
| Doi | 10.3389/fimmu.2021.738958 | Citation | Le PT, et al. (2021) Targeting Cbx3/HP1gamma Induces LEF-1 and IL-21R to Promote Tumor-Infiltrating CD8 T-Cell Persistence. Front Immunol 12:738958 |
| abstractText | Immune checkpoint blockade (ICB) relieves CD8(+) T-cell exhaustion in most mutated tumors, and TCF-1 is implicated in converting progenitor exhausted cells to functional effector cells. However, identifying mechanisms that can prevent functional senescence and potentiate CD8(+) T-cell persistence for ICB non-responsive and resistant tumors remains elusive. We demonstrate that targeting Cbx3/HP1gamma in CD8(+) T cells augments transcription initiation and chromatin remodeling leading to increased transcriptional activity at Lef1 and Il21r. LEF-1 and IL-21R are necessary for Cbx3/HP1gamma-deficient CD8(+) effector T cells to persist and control ovarian cancer, melanoma, and neuroblastoma in preclinical models. The enhanced persistence of Cbx3/HP1gamma-deficient CD8(+) T cells facilitates remodeling of the tumor chemokine/receptor landscape ensuring their optimal invasion at the expense of CD4(+) Tregs. Thus, CD8(+) T cells heightened effector function consequent to Cbx3/HP1gamma deficiency may be distinct from functional reactivation by ICB, implicating Cbx3/HP1gamma as a viable cancer T-cell-based therapy target for ICB resistant, non-responsive solid tumors. |
