免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:TIL cell therapy in HIV positive patient with metastatic melanoma: case report.
TIL cell therapy in HIV positive patient with metastatic melanoma: case report.
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TIL(肿瘤浸润淋巴细胞)疗法是一种新兴治疗方法,适用于免疫检查点抑制剂治疗后疾病进展的转移性黑色素瘤患者。然而,长期以来,病毒受到良好控制的HIV感染者一直被排除在过继细胞疗法临床试验之外,因此该人群的安全性、耐受性、免疫影响和肿瘤学应答仍不明确。本文报告目前已知首例接受TIL疗法治疗免疫治疗难治性转移性黑色素瘤的病毒学抑制HIV感染者。患者为37岁男性,长期接受抗逆转录病毒治疗(ART),患BRAF-V600E突变转移性黑色素瘤,累及巨大腋窝病灶和肺转移;尽管接受抗PD-1治疗、联合检查点阻断及BRAF/MEK靶向治疗,疾病仍快速进展。TIL治疗前,患者仅有轻微治疗相关毒性,并间歇检测到低水平HIV病毒血症。
经多学科评估后,患者接受TIL采集、淋巴细胞清除化疗、lifileucel输注和大剂量白细胞介素2(IL-2)治疗。TIL治疗的毒性符合预期且可耐受,包括1级细胞因子释放综合征,以及IL-2相关3级低血压(需短期升压药支持)。第44天影像显示部分缓解:肺转移灶减少,腋窝病灶稳定。至第86天观察到疾病进展。治疗期间CD4计数显著波动,但至第100天病毒学抑制恢复。本病例表明,对病毒控制良好的HIV感染者可行实施TIL治疗,毒性可管理并可获得早期影像学应答。研究结果强调,应在细胞疗法试验中前瞻性纳入HIV感染者,以更好描述安全性、免疫动态及持久获益的预测因素。
Tumor-infiltrating lymphocyte (TIL) therapy is an emerging treatment for patients with metastatic melanoma whose disease has progressed on immune checkpoint inhibitors.
However, individuals living with well-controlled human immunodeficiency virus (HIV) have historically been excluded from clinical trials evaluating adoptive cell therapies, leaving uncertainty regarding safety, tolerability, immune effects, and oncologic response in this population.
We present the first known case of a patient with virologically suppressed HIV receiving TIL therapy for immunotherapy-refractory metastatic melanoma. A 37-year-old man with long-standing HIV on antiretroviral therapy (ART) developed rapidly progressive, BRAF-V600E mutant metastatic melanoma involving bulky axillary disease and pulmonary metastases despite anti-PD-1 therapy, combined checkpoint blockade, and BRAF/MEK-targeted therapy. His course prior to TIL therapy was notable for minimal treatment-related toxicities and intermittent detectable low-level HIV viremia. After multidisciplinary review, he underwent TIL harvest followed by lymphodepleting chemotherapy, lifileucel infusion, and high-dose interleukin-2 (IL-2).
TIL therapy was tolerated with expected toxicities, including grade 1 cytokine release syndrome and IL-2-associated grade 3 hypotension requiring brief vasopressor support. At day 44, imaging demonstrated a partial response with decreased pulmonary metastases and stabilization of axillary disease.
Progression of disease was observed by day 86. CD4 counts fluctuated markedly throughout treatment, though virologic suppression was ultimately restored by day 100. This case demonstrates that TIL therapy can be feasibly administered to a patient with well-controlled HIV, with manageable toxicity and early radiographic response.
These findings underscore the need for prospective inclusion of people living with HIV in cellular therapy trials to better characterize safety, immune dynamics, and predictors of durable benefit.
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