2020年5月19日 · Here, we defined a four-cell-stage developmental framework for Tex cells. Two TCF1 + progenitor subsets were identified, one tissue restricted and quiescent and one more blood accessible, that gradually lost TCF1 as it divided and …

CD8+ T 细胞耗竭是当前抗癌免疫疗法的主要障碍。 尽管如此，耗尽的 CD8+ T 细胞 (Tex) 的发育生物学仍然不明确，限制了旨在“重振”Tex 细胞的策略的改进。 在这里，我们为 Tex 细胞定义了一个四细胞阶段的发展框架。 鉴定了两个 TCF1+ 祖细胞亚群，一个组织受限且处于静止状态，另一个是可进入的血液，随着 TCF1 分裂并转化为第三个中间 Tex 亚群，逐渐失去了 TCF1。 这个中间子集重新参与了一些效应生物学，并在 PD-L1 阻断后增加，但最终转化为第四个最终耗尽的 …

2023年12月12日 · We examined epigenetic transitions between Tex cell subsets and revealed a reciprocally antagonistic circuit between Stat5a and Tox. Stat5 directed Tex int cell formation and re-instigated partial effector biology during this Texprog -to-Tex int cell transition.

Reversing CD8+ T cell exhaustion is a major challenge of cancer immunotherapy. Yet, the epigenetic stability of the exhaustion program remains a key hinderance. Beltra et al. identify the transcription factor Stat5 as a key axis to exploit for rewiring exhausted CD8+ T cells toward more durably protective states.

MS Abdel-Hakeem, S Manne, JC Beltra, E Stelekati, Z Chen, K Nzingha, ... Nature immunology 22 (8), 1008-1019, 2021. 193: 2021: In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer. Z Chen, E Arai, O Khan, Z Zhang, SF Ngiow, Y …

Beltra et al. define a hierarchical developmental pathway for CD8+ T cell exhaustion, revealing four stages and multistep transcriptional and epigenetic dynamics underlying subset transitions and subset-associated biological changes. CD8+ T cell exhaustion is a major barrier to current anti-cancer immunotherapies.

Beltra JC, Manne S, Abdel-Hakeem MS, Kurachi M, Giles JR, Chen Z, Casella V, Ngiow SF, Khan O, Huang YJ, Yan P, Nzingha K, Xu W, Amaravadi RK, Xu X, Karakousis GC, Mitchell TC, Schuchter LM, Huang AC, Wherry EJ. Immunity. 2020 May 19;52(5):825-841.e8. doi: 10.1016/j.immuni.2020.04.014

2020年5月19日 · In this issue of Immunity, Beltra et al. (2020) map out a differentiation trajectory of T cell exhaustion, delineating hierarchical developmental relationships and providing insight into the molecular mechanisms that control the journey …

Beltra et al. define a hierarchical developmental pathway for CD8 + T cell exhaustion, revealing four stages and multistep transcriptional and epigenetic dynamics underlying subset transitions and subset-associated biological changes.

2023年12月20日 · Based on the enhanced accumulation and effector-NK-like features of STAT5CA cells, Beltra et al. evaluated their therapeutic potential in mice with established B16 tumors expressing the viral target antigen. While control cells only slightly delayed tumor growth, STAT5CA cells substantially decreased tumor burdens, resulting in enhanced ...