工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Focusing on CD8(+) T-cell phenotypes: improving solid tumor therapy.
Focusing on CD8(+) T-cell phenotypes: improving solid tumor therapy.
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强效的CD8+ T细胞在识别肿瘤细胞和对抗实体瘤中发挥着至关重要的作用。T细胞如何有效识别和靶向肿瘤抗原,以及如何在“排斥”实体瘤微环境中维持活性,是主要关注点。近期对CD8+T细胞免疫轨迹和寿命的理解进展,为设计更优化的抗肿瘤免疫治疗方案提供了指导。在此,我们综述了新发现的增强CD8+T细胞对抗实体瘤功能的方法,重点关注优化T细胞受体(TCR)表达、改善工程化T细胞的抗原识别、增强TCR-CD3复合物的信号转导、诱导多克隆功能性T细胞向肿瘤归巢、逆转慢性抗原刺激下的T细胞耗竭,以及重编程T细胞的能量和代谢途径。我们还讨论了如何参与CD8+T细胞的表观遗传改变,以调控抗肿瘤应答的两个关键指标,即有效性和持久性。
Vigorous CD8 + T cells play a crucial role in recognizing tumor cells and combating solid tumors. How T cells efficiently recognize and target tumor antigens, and how they maintain the activity in the "rejection" of solid tumor microenvironment, are major concerns. Recent advances in understanding of the immunological trajectory and lifespan of CD8 + T cells have provided guidance for the design of more optimal anti-tumor immunotherapy regimens.
Here, we review the newly discovered methods to enhance the function of CD8 + T cells against solid tumors, focusing on optimizing T cell receptor (TCR) expression, improving antigen recognition by engineered T cells, enhancing signal transduction of the TCR-CD3 complex, inducing the homing of polyclonal functional T cells to tumors, reversing T cell exhaustion under chronic antigen stimulation, and reprogramming the energy and metabolic pathways of T cells.
We also discuss how to participate in the epigenetic changes of CD8 + T cells to regulate two key indicators of anti-tumor responses, namely effectiveness and persistence.
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