Percutaneous ablative cryoimmunotherapy for micrometastaic abscopal effect: No complications
Percutaneous ablative cryoimmunotherapy for micrometastaic abscopal effect: No complications
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DOI：
10.1016/j.cryobiol.2018.04.013
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发表时间：
2018-06-01
期刊：
影响因子：
2.7
通讯作者：
Matteo, Jerry
中科院分区：
文献类型：
--
作者：
Soule, Erik;Bandyk, Mark;Matteo, Jerry
最近的研究表明，nivolumab是一种针对被称为程序性死亡1(PD-1)的免疫调节蛋白的单抗，对转移性肾癌有疗效。PD-1是一种表达在T细胞上的跨膜蛋白，可抑制与其配体结合时的激活，各种癌症可能会副肿瘤地分泌PD-1。通过nivolumab抑制PD-1信号可能会在免疫抑制的肿瘤微环境中使肿瘤特异性T淋巴细胞增敏。全身清除微转移需要强大的肿瘤抗原刺激的T细胞的激活和增殖。冷冻消融会溶解肿瘤细胞膜，但细胞内的肿瘤抗原保持不变，以供效应器系统识别，同时局部消除允许的T细胞亚型。这一单一病例报告描述了CT引导下经皮冷消融治疗转移性肾细胞癌，并局部应用nivolumab，以同时去除原发肿瘤，增强效应T细胞对肿瘤抗原的敏感性，并增强对已建立的转移的全身免疫反应。随访1个月，PET扫描显示两个较小的骨转移灶摄取减少，最小的病灶完全消除。最大的骨转移灶大小略有缩小，摄取略有增加。患者提出的髋部疼痛的主诉被取消，允许她恢复独立行走。CT引导下的经皮冷冻消融术是一种微创的治疗方法，它保留了肿瘤抗原，随后将这些抗原呈递给肿瘤特异性T细胞；可以引导它们分化为细胞毒性T细胞，并在手术时局部给予免疫刺激药物治疗，以促进它们的增殖。
Recent studies have shown efficacy of nivolumab, a monoclonal antibody specific for an immunoregulatory protein termed programmed death 1 (PD-1), against metastatic renal cell carcinoma. PD-1 is a transmembrane protein expressed on T cells that suppresses activation upon binding to its ligands, which may be secreted paraneoplastically by various cancers. Inhibition of PD-1 signaling via nivolumab may sensitize tumor-specific T lymphocytes in the immunosuppressive tumor microenvironment. Systemic elimination of micrometastases requires robust activation and proliferation of tumor antigen stimulated T cells. Cryoablation lyses tumor cell membranes but leaves intracellular tumor antigens intact for recognition by effectors systemically, while eliminating permissive T cell subtypes locally. This single case report describes CT-guided percutaneous cryoablation of a metastatic renal cell carcinoma with local administration of nivolumab to simultaneously debulk the primary tumor, sensitize effector T cells against tumor antigens, and augment the systemic immune response elicited against established metastases. One month follow up PET scan revealed decreased uptake in the two smaller metastatic bone lesions with the smallest lesion completely eliminated. The largest metastatic bone lesion was slightly decreased in size and exhibited slightly increased uptake. The patient's presenting complaint of hip pain was abrogated, allowing her to resume independent ambulation. CT-guided percutaneous cryoablation is minimally invasive and preserves tumor antigens, which are subsequently presented to tumor-specific T cells; their differentiation into cytotoxic T cells may be guided and their proliferation may be augmented by local administration of immunostimulatory pharmacotherapy at the time of the procedure.