dc.contributor.author | Le, Phuong T. | |
dc.contributor.author | Ha, Ngoc | |
dc.contributor.author | Tran, Ngan K. | |
dc.contributor.author | Newman, Andrew G. | |
dc.contributor.author | Esselen, Katharine M. | |
dc.contributor.author | Dalrymple, John L. | |
dc.contributor.author | Schmelz, Eva M. | |
dc.contributor.author | Bhandoola, Avinash | |
dc.contributor.author | Xue, Hai-Hui | |
dc.contributor.author | Singh, Prim B. | |
dc.contributor.author | Thai, To-Ha | |
dc.date.accessioned | 2021-12-20T09:54:07Z | |
dc.date.available | 2021-12-20T09:54:07Z | |
dc.date.issued | 2021-10-06 | |
dc.identifier.citation | Le, P. T., Ha, N., Tran, N. K., Newman, A. G., Esselen, K. M., Dalrymple, J. L., Schmelz, E. M., Bhandoola, A., Xue, H. H., Singh, P. B., & Thai, T. H. (2021). Targeting Cbx3/HP1γ Induces LEF-1 and IL-21R to Promote Tumor-Infiltrating CD8 T-Cell Persistence. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.738958 | en_US |
dc.identifier.uri | http://nur.nu.edu.kz/handle/123456789/5932 | |
dc.description.abstract | 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/HP1γ 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/HP1γ-deficient CD8+ effector T cells to persist and control ovarian cancer, melanoma, and neuroblastoma in preclinical models. The enhanced persistence of Cbx3/HP1γ-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/HP1γ deficiency may be distinct from functional reactivation by ICB, implicating Cbx3/HP1γ as a viable cancer T-cell-based therapy target for ICB resistant, non-responsive solid tumors | en_US |
dc.language.iso | en | en_US |
dc.publisher | Frontiers in Immunology | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/us/ | * |
dc.subject | Cbx3/HP1γ | en_US |
dc.subject | LEF-1 | en_US |
dc.subject | IL-21 receptor | en_US |
dc.subject | CD8+ T-cell persistence | en_US |
dc.subject | ovarian cancer | en_US |
dc.subject | melanoma | en_US |
dc.title | TARGETING CBX3/HP1Γ INDUCES LEF-1 AND IL-21R TO PROMOTE TUMOR-INFILTRATING CD8 T-CELL PERSISTENCE | en_US |
dc.type | Article | en_US |
workflow.import.source | science |
The following license files are associated with this item: