Section of Urology, Department of Surgery, University of Chicago, Chicago, IL, USA.
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
J Immunother Cancer. 2019 Mar 11;7(1):66. doi: 10.1186/s40425-019-0546-8.
Clinically localized renal cell carcinoma is treated primarily with surgery followed by observation or adjuvant sunitinib in selected high-risk patients. The checkpoint inhibitor immunotherapeutic agents nivolumab and ipilimumab have recently shown a survival benefit in the first-line metastatic setting. To date, there have been no reports on the response of localized renal cancer to modern immunotherapy. We report a remarkable response of an advanced tumor thrombus to combined immunotherapy which facilitated curative-intent resection of the non-responding primary renal tumor. We characterized the tumor microenvironment within the responding and non-responding tumors.
A 54-year-old female was diagnosed with a locally advanced clear cell renal cell carcinoma with a level IV tumor thrombus of the vena cava. She was initially deemed unfit for surgical resection due to poor performance status. She underwent neoadjuvant immunotherapy with nivolumab and ipilimumab with a complete response of the vena cava and renal vein tumor thrombus, but had stable disease within her renal mass. She underwent complete surgical resection with negative margins and remains disease-free longer than 1 year after her diagnosis with no further systemic therapy. Notably, pathologic analysis showed a complete response within the vena cava and renal vein, but substantial viable cancer remained in the kidney. Multichannel immunofluorescence was performed and showed marked infiltration of immune cells including CD8 T cells and Batf3 dendritic cells in the thrombus, while the residual renal tumor showed a non-T cell-inflamed phenotype.
Preoperative immunotherapy with nivolumab and ipilimumab for locally advanced clear cell renal cancer resulted in a complete response of an extensive vena cava tumor thrombus, which enabled curative-intent resection of a non-responding primary tumor. If validated in larger cohorts, preoperative immunotherapy for locally advanced renal cell carcinoma may ultimately impact surgical planning and long-term prognosis.
局限性肾细胞癌主要通过手术治疗，然后在选择的高危患者中观察或辅助使用舒尼替尼。检查点抑制剂免疫治疗药物纳武利尤单抗和伊匹单抗最近在一线转移性环境中显示出生存获益。迄今为止，尚无关于局部肾肿瘤对现代免疫疗法反应的报道。我们报告了一例晚期肿瘤血栓对联合免疫治疗的显著反应，这使得能够对非反应性原发性肾肿瘤进行治愈性切除。我们对反应性和非反应性肿瘤内的肿瘤微环境进行了特征描述。
一名 54 岁女性被诊断为局部晚期透明细胞肾细胞癌，伴有 IV 级腔静脉肿瘤血栓。由于身体状况不佳，她最初被认为不适合手术切除。她接受了纳武利尤单抗和伊匹单抗的新辅助免疫治疗，肿瘤完全缓解，腔静脉和肾静脉肿瘤血栓消退，但肾脏肿块内仍为稳定疾病。她接受了完全切除手术，切缘阴性，并且在诊断后 1 年以上仍无疾病，没有进一步的系统治疗。值得注意的是，病理分析显示腔静脉和肾静脉内完全缓解，但肾脏中仍有大量存活的癌症。进行了多通道免疫荧光分析，显示血栓中有大量免疫细胞浸润，包括 CD8 T 细胞和 Batf3 树突状细胞，而残留的肾肿瘤表现出非 T 细胞浸润表型。
术前用纳武利尤单抗和伊匹单抗对局部晚期透明细胞肾细胞癌进行免疫治疗，导致广泛的腔静脉肿瘤血栓完全缓解，从而能够对非反应性原发性肿瘤进行治愈性切除。如果在更大的队列中得到验证，局部晚期肾细胞癌的术前免疫治疗最终可能会影响手术计划和长期预后。
Zotero 插件
