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晚期胆囊癌根治术后多发肝转移患者接受免疫治疗联合抗血管生成药物的完全缓解:一例报告

Complete response to immunotherapy combined with an antiangiogenic agent in multiple hepatic metastases after radical surgery for advanced gallbladder cancer: a case report.

作者信息

Rao Jianhua, Xia Jinguo, Yang Wenjie, Wu Chen, Sha Bowen, Zheng Qitong, Cheng Feng, Lu Ling

机构信息

Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

出版信息

Ann Transl Med. 2020 Dec;8(23):1609. doi: 10.21037/atm-20-4420.

Abstract

Most advanced gallbladder cancers (GBCa) are unresectable or metastatic once diagnosed, and even patients who undergo surgery have a high risk of recurrence and metastasis. Immunotherapy, especially immune checkpoint inhibitors (ICIs), combined with an antiangiogenic agent, is an emerging prospective treatment for GBCa. However, the efficacy and safety of this combination therapy have not yet been investigated. We report the case of a 70-year-old female patient with recurrent metastatic GBCa (stage IVB) after radical surgery. Immunohistochemical examination revealed that 10% of the tumor cells expressed programmed cell death protein-1 (PD-1) and programmed cell death receptor ligand 1 (PD-L1). Whole-exome sequencing showed cancer tissues with a low tumor mutational burden (TMB) and microsatellite stability (MSS). The patient received Camrelizumab (200 mg, every three weeks) and Apatinib (40 mg/d). The clinical and immunological responses were observed, and the patient achieved a complete response after five cycles. This is the first case describing the efficacy and safety of Camrelizumab plus Apatinib in a GBCa patient with weak PD-1 and PD-L1 expression, and low TMB and MSS. The treatment had a tolerable safety profile and a complete response in the patient. Also, we found that the cluster of differentiation (CD)16+CD56+natural killer (NK) cell ratio in peripheral blood was increased after the combined treatment. Immunotherapy with antiangiogenic drugs may be a potential treatment option for patients with recurrent GBC or GBCa.

摘要

大多数晚期胆囊癌(GBCa)一旦确诊即为不可切除或转移性,即使接受手术的患者也有很高的复发和转移风险。免疫疗法,尤其是免疫检查点抑制剂(ICIs)联合抗血管生成药物,是一种新兴的GBCa前瞻性治疗方法。然而,这种联合疗法的疗效和安全性尚未得到研究。我们报告了一例70岁女性患者,在根治性手术后出现复发性转移性GBCa(IVB期)。免疫组织化学检查显示,10%的肿瘤细胞表达程序性细胞死亡蛋白-1(PD-1)和程序性细胞死亡受体配体1(PD-L1)。全外显子测序显示癌组织的肿瘤突变负荷(TMB)低且微卫星稳定(MSS)。该患者接受了卡瑞利珠单抗(200mg,每三周一次)和阿帕替尼(40mg/d)治疗。观察到临床和免疫反应,患者在五个周期后达到完全缓解。这是第一例描述卡瑞利珠单抗联合阿帕替尼在PD-1和PD-L1表达弱、TMB和MSS低的GBCa患者中的疗效和安全性的病例。该治疗具有可耐受的安全性,且患者获得了完全缓解。此外,我们发现联合治疗后外周血中分化簇(CD)16+CD56+自然杀伤(NK)细胞比例增加。抗血管生成药物免疫疗法可能是复发性GBC或GBCa患者的一种潜在治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2e/7791255/efd6d074a9ec/atm-08-23-1609-f1.jpg

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