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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Autologous Tumor-Infiltrating Lymphocyte Mono-Therapy Can Rapidly Shrank Tumor in Asian Patient with Stage III/IV Cervical Cancer: Two Cases Report.
Autologous Tumor-Infiltrating Lymphocyte Mono-Therapy Can Rapidly Shrank Tumor in Asian Patient with Stage III/IV Cervical Cancer: Two Cases Report.
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这些结果提示,TILs 单一疗法对于亚洲晚期转移性宫颈癌患者,即使伴有严重骨髓抑制,也可能是一种有前景的治疗策略。TILs 输注可诱导持续性及长期系统性免疫应答,逆转外周 CD4+T 和 CD8+T 百分比,提示 TILs 输注增强了细胞毒性 T 细胞应答,这与这些患者的临床反应一致。试验注册号:NCT05366478。
TIL(肿瘤浸润淋巴细胞)(TILs)疗法是最有前景的过继性T细胞疗法之一,已在多种实体恶性肿瘤中展现出良好的临床疗效。然而,亚洲复发性宫颈癌患者接受TILs单一疗法的临床应答尚未得到充分报道。病例介绍:本文报道了两例诊断为转移性宫颈癌且在接受多种常规治疗后出现肿瘤进展的患者。其中一例患者有化疗后严重骨髓抑制的病史。患者接受了淋巴细胞清除治疗,方案为环磷酰胺(30mg/kg)连续2天,随后氟达拉滨(25mg/m²)连续5天,在接受静脉自体TILs输注前约24小时完成。随后这两例患者接受高剂量IL-2治疗10天,以维持T细胞存活和增殖。患者1在TILs输注后6周达到临床部分缓解(PR),12周随访时肿瘤缩小33%;患者2在治疗后6周评估为疾病稳定(SD)。观察到轻度且可管理的不良事件,在TILs治疗后不久即消退。一项对外周血细胞计数和细胞因子分泌的时间进程研究证实了输注TILs的持续存在及长期免疫应答。
INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) therapy is one of the most promising adoptive T cell therapies, which has shown great clinical efficacy against several solid malignancies. Nevertheless, clinical response to TILs mono-therapy in Asian patients with recurrent cervical cancer has not been well reported. CASE PRESENTATION: Here, we report two patients who were diagnosed with metastatic cervical cancer and tumor progression following multiple conventional treatments. In particular, one of the patients has a history of severe myelosuppression after chemotherapy. The patients received lymphodepletion therapy, which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m 2 ) for 5 days, approximately 24 hr before receiving intravenous autologous TILs infusion. These two patients then received high doses of IL-2 for 10 days with the purpose of maintaining T cell survival and proliferation. Patient 1 experienced clinical partial response (PR) at 6 weeks post TILs infusion and a 33% tumor shrinkage at 12 weeks follow-up, and patient 2 was evaluated as stable disease (SD) at 6 weeks post treatment. Mild and manageable adverse events were observed and soon subsided after the TILs treatment. A time-course study examining the peripheral blood cell count and cytokine secretion demonstrated the persistence of infused TILs and long-term immune response. CONCLUSION: These results suggest that TILs mono-therapy can be a promising treatment strategy for Asian patients with late-stage metastatic cervical cancer even with severe myelosuppression. TILs infusion can induce persistence and a long-term systematic immune response that reversed peripheral CD4+T and CD8+T percentages implying that TILs infusion increased cytotic T cell responses, which is consistent with clinical responses in these patients. Trial registration number: NCT05366478.
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