CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
受限的 T 细胞迁移调控程序性死亡受体 1 表达
英文原题：Confined T cell migration controls programmed cell death 1 expression.
查看英文原题
Confined T cell migration controls programmed cell death 1 expression.
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中文摘要
T细胞免疫检查点表达与功能障碍此前被认为仅由分子线索决定。我们利用微生理系统和体内模型发现，通过受限孔隙的跨内皮迁移可在数分钟内诱导CD8+ T细胞表面免疫检查点标志物中程序性细胞死亡1的急性丢失，这一过程通过泛素介导的蛋白酶体降解实现，并与适应性和功能增强相对应。这种印记及其程序性细胞死亡1丢失的潜在机制在物种间保守，并适用于人类TIL和CAR-T 细胞，且与人类黑色素瘤的疾病结局相关。我们的研究确立了T细胞在免疫监视过程中所穿越的多样组织景观，特别是跨内皮迁移，作为一种机械免疫调节形式，并揭示了一种机械调节策略，以提高工程化或患者来源T细胞用于过继免疫治疗的质量和持久性。
展开英文摘要原文
T cell immune checkpoint expression and dysfunction are attributed solely to molecular cues.
We discover using microphysiological systems and in vivo models that transmigration through confined pores induces acute loss of programmed cell death 1 within minutes of surface immune checkpoint markers on CD8+ T cells through ubiquitin-mediated proteasomal degradation, corresponding with enhanced fitness and function. Such imprints and its underlying mechanism of programmed cell death 1 loss are conserved across species and applicable to human TIL and CAR T cells, and are correlative with disease outcomes in human melanoma.
Our findings establish the diverse tissues landscapes that T cells traverse during immunosurveillance, and specifically transmigration, as a form of mechanical immune regulation, and reveal a mechano-modulatory strategy to improve the quality and persistence of engineered or patient-derived T cells for adoptive immunotherapy.
论文信息
- 作者
- Alapan Y、Kim J、Min K、Shih A、Lucas SN、Yoon T、Archer PA、Lin HK
- 文献类型
- 预印本
- 期刊
- bioRxiv : the preprint server for biology2026 Jul 9
- 原文标识
- PubMed 42465295 · DOI 10.64898/2026.07.03.736145