敲除 Satb1 重编程耗竭 CD8(+) T 细胞亚群的分化轨迹以增强抗肿瘤免疫

In this study, we explore the role of special AT-rich sequence-binding protein 1 (SATB1) in the differentiation of Tex-int cells from their precursors. We observed downregulation of SATB1 during Tpex-to-Tex-int differentiation in tumors. Notably, the genetic ablation of Satb1 in T cells markedly expanded the population of tumor-infiltrating CD8 + T cells (CD8 + TILs).

Ablating Satb1 not only promoted the differentiation of Tex-int cells from Tpex cells within the tumor microenvironment but also remodeled T cell differentiation in tumor-draining lymph nodes (TdLNs) by expanding the Tpex pool from tumor-specific memory CD8 + T cells (T TSM ) and driving the Tpex1 to Tpex2 transition, thereby augmenting Tex-int production in tumors. Although early-stage Tex-int cells in Satb1 -deficient mice displayed transient functional impairment relative to controls, this difference was no longer evident in late-stage tumors, where sustained Tex-int accumulation correlated with significantly suppressed tumor growth and prolonged survival. DISCUSSION: Our results identify SATB1 as a pivotal regulator of exhausted CD8 + T cell subset differentiation and suggest its targeting as a promising strategy to expand the Tex-int population for enhanced cancer immunotherapy.