单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
TIL(肿瘤浸润淋巴细胞)过继细胞治疗可在转移性黑色素瘤中诱导持久缓解,然而在体外扩增过程中及回输后,调控肿瘤反应性T细胞命运的克隆和转录动态仍知之甚少。
英文原题:Tumor-infiltrating lymphocytes mediate complete and durable remission in a patient with NY-ESO-1 expressing prostate cancer.
在分别输注1.4×10^9、2.0×10^9和8.0×10^9个T细胞的3次TIL治疗后,观察到完全且持久的肿瘤缓解,现已持续超过3.5年。
过继转移自体肿瘤特异性淋巴细胞是晚期恶性肿瘤患者的一种可行治疗方法。在此,我们报告一例转移性激素难治性纽约食管鳞状细胞癌1(NY-ESO-1)表达前列腺癌患者,接受体外扩增的TIL(肿瘤浸润淋巴细胞)(TILs)联合IL-2和免疫检查点阻断治疗。在分别输注1.4×10^9、2.0×10^9和8.0×10^9 T细胞的三次TIL输注后,观察到完全且持久的肿瘤缓解,目前已持续超过3.5年。与临床进展相关的免疫学指标是肿瘤驱动的NY-ESO-1血清抗体下降和前列腺特异性抗原降至<0.01 g/L。TILs对癌-睾丸抗原NY-ESO-1、个体肿瘤突变蛋白(如PRPF8、TRPS1)和雄激素受体剪接变体12具有反应性。
Adoptive transfer of autologous tumor-specific lymphocytes represents a viable treatment method for patients with advanced malignancies. Here, we report a patient's case with metastatic hormone-refractory New York esophageal squamous cell carcinoma 1 (NY-ESO-1) expressing prostate cancer treated with in vitro expanded tumor-infiltrating lymphocytes (TILs) in conjunction with IL-2 and immune-checkpoint blockade. Complete and durable tumor remission was observed after three TIL infusions consisting of 1.4 10 9 , 2.0 10 9 , and 8.0 10 9 T cells, respectively, lasting now for more than 3.5 years. Immunological correlates to the clinical development were the decrease of tumor-driven NY-ESO-1 serum antibody and the drop of prostate-specific antigen to <0.01 g/L. TILs were reactive against cancer-testis antigen NY-ESO-1, individual tumor mutational proteins (eg, PRPF8, TRPS1), and the androgen receptor splice variant 12.
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