Soule Erik, Bandyk Mark, Matteo Jerry
Department of Interventional Radiology, UF Health Jacksonville, University of Florida, 655 W 8th, St., Jacksonville, FL, 32209, USA.
Department of Urology, UF Health Jacksonville, University of Florida, 655 W 8th, St., Jacksonville, FL, 32209, USA.
Cryobiology. 2018 Jun;82:22-26. doi: 10.1016/j.cryobiol.2018.04.013. Epub 2018 Apr 19.
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.
近期研究表明，纳武单抗（一种针对名为程序性死亡1（PD-1）的免疫调节蛋白的单克隆抗体）对转移性肾细胞癌有效。PD-1是一种表达于T细胞上的跨膜蛋白，其与配体结合后会抑制激活，而这些配体可能由各种癌症旁分泌产生。通过纳武单抗抑制PD-1信号传导可能会使免疫抑制性肿瘤微环境中的肿瘤特异性T淋巴细胞敏感化。全身清除微转移灶需要肿瘤抗原刺激的T细胞进行强有力的激活和增殖。冷冻消融可裂解肿瘤细胞膜，但使细胞内肿瘤抗原保持完整，以便全身效应细胞识别，同时在局部消除允许性T细胞亚型。本单病例报告描述了CT引导下经皮冷冻消融转移性肾细胞癌并局部给予纳武单抗，以同时缩小原发性肿瘤体积、使效应T细胞对肿瘤抗原敏感化，并增强针对已形成转移灶引发的全身免疫反应。1个月后的PET扫描显示，两个较小的转移性骨病灶摄取减少，最小的病灶已完全消除。最大的转移性骨病灶大小略有减小，摄取略有增加。患者最初的髋部疼痛主诉已消除，使其能够恢复独立行走。CT引导下经皮冷冻消融是微创的，可保留肿瘤抗原，随后将其呈递给肿瘤特异性T细胞；在手术时局部给予免疫刺激药物治疗可引导它们分化为细胞毒性T细胞，并增强其增殖。
