肿瘤细胞治疗研究
英文原题：The evolution of cellular therapies in sarcoma: Breakthroughs, challenges, and future directions.
细胞疗法是晚期癌症免疫治疗中一个前景广阔的领域，包括T细胞受体（TCR）疗法、嵌合抗原受体（CAR）T细胞疗法、TIL（肿瘤浸润淋巴细胞）疗法和自然杀伤（NK）细胞疗法。肉瘤因其分子复杂性和免疫抑制性肿瘤微环境（TME）而带来独特挑战。
细胞疗法是晚期癌症免疫治疗中一个有前景的领域，包括 T 细胞受体（TCR）疗法、嵌合抗原受体（CAR）T 细胞疗法、TIL（肿瘤浸润淋巴细胞）疗法和自然杀伤（NK）细胞疗法。肉瘤由于其分子复杂性和免疫抑制性肿瘤微环境（TME）而带来独特挑战。靶向 NY-ESO-1、MAGE-A4 和 PRAME 等抗原的 TCR 疗法已显示出疗效，FDA 加速批准靶向 MAGE-A4 的 afamitresgene autoleucel 用于滑膜肉瘤即为突出例证。靶向 HER2、GD2 和 B7-H3 的 CAR-T 细胞疗法，以及 TIL 和 NK 细胞疗法也正在研究中。然而，许多疗法仍处于临床开发的早期阶段，其有效性可能因肉瘤亚型而异。克服免疫抑制性 TME、抗原逃逸、T 细胞持久性不足和脱靶毒性等挑战，对于改善肉瘤患者的结局至关重要。本综述总结了细胞疗法的演变、正在进行的研究、挑战以及该领域的未来方向。
Cellular therapies representa promising area of immunotherapy for advanced cancers,therapies including T cell receptor (TCR) therapies, chimeric antigen receptor (CAR) T cell therapies, tumor-infiltrating lymphocyte (TIL) therapies, and natural killer (NK) cell therapies.Sarcomas pose unique challenges due to their molecular complexity and immunosuppressive tumor microenvironment (TME). TCRtherapiesargeting antigens likeNY-ESO-1, MAGE-A4, and PRAME have shown efficacy, highlighted by the FDA's accelerated approval of afamitresgene autoleucel targeting MAGE-A4 for synovial sarcoma.CAR-T cell therapies targeting HER2, GD2, and B7-H3, along with TIL, and NK cell therapies are also under investigation.However, many are in early stages of clinical development, and their effectiveness may vary by sarcoma subtype. Overcoming challenges such as immunosuppressive TME, antigen escape, lack of T-cell persistence, and off-target toxicities is crucial to improving outcomes for sarcoma patients. This review summarizes the evolution of cellular therapies,ongoing research, challenges, and future directions in this field.
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