Zhu Qi, Li Jiajia, Liu Nan, Han Lu, Wu Zhiqiang, Wang Yao, Lin Xin, Wei Jianshu, Han Weidong
Department of Biotherapy, the First Medical Center, Chinese PLA General Hospital, Beijing, China.
Changping Laboratory, Beijing, China.
Cell Mol Immunol. 2025 Jul 4. doi: 10.1038/s41423-025-01314-6.
CAR-T-cell therapy has made significant strides in treating hematological malignancies, yet its efficacy is often hampered by suboptimal T-cell functionality, marked by weak antitumor capabilities and a lack of durability. The immunological synapse, a key determinant of T-cell function, is influenced by the CD58-CD2 axis. The dynamic regulation of CD2 expression on T cells impacts the quality of CAR-mediated immunological synapses, affecting CAR-T-cell functional outcomes and differentiation. Our study demonstrated that CD2 expression levels are closely linked to the quality of immunological synapses formed by CAR-T cells and their antitumor potency. Exogenous CD2 supplementation enhances the ability of CAR-T cells to form high-quality synapses, reduces T-cell exhaustion, and increases sustained antitumor efficacy. Additionally, ectopic CD2 expression increases CAR-T-cell sensitivity to low-density antigens. Thus, replenishing CD2 in CAR-T cells is a promising strategy to increase the therapeutic efficacy of CAR-T-cell therapy.
嵌合抗原受体T细胞（CAR-T）疗法在治疗血液系统恶性肿瘤方面取得了重大进展，但其疗效常常受到T细胞功能欠佳的阻碍，表现为抗肿瘤能力较弱且缺乏持久性。免疫突触是T细胞功能的关键决定因素，受CD58-CD2轴的影响。T细胞上CD2表达的动态调节会影响CAR介导的免疫突触质量，进而影响CAR-T细胞的功能结果和分化。我们的研究表明，CD2表达水平与CAR-T细胞形成的免疫突触质量及其抗肿瘤效力密切相关。外源性补充CD2可增强CAR-T细胞形成高质量突触的能力，减少T细胞耗竭，并提高持续抗肿瘤疗效。此外，异位表达CD2可增加CAR-T细胞对低密度抗原的敏感性。因此，在CAR-T细胞中补充CD2是提高CAR-T细胞疗法治疗效果的一种有前景的策略。
