College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Cells. 2021 Aug 15;10(8):2096. doi: 10.3390/cells10082096.
Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options.
肝胆癌包括肝细胞癌(HCC)、胆管癌(CCA)和胆囊癌(GBC),是一种致命的癌症,治疗选择有限。根治性治疗通常涉及手术,但复发很常见,许多患者患有晚期疾病,无法手术。免疫疗法是改善预后的一种有前途的方法,但肝胆癌特征性的免疫抑制肿瘤微环境阻碍了这种治疗方法的发展和实施。目前正在研究的免疫疗法包括免疫检查点抑制剂(ICI)、免疫细胞过继转移、双特异性抗体、疫苗和溶瘤病毒。程序性细胞死亡蛋白 1(PD-1)和细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)是两种已在 HCC 中证明有效的 ICI,并且正在临床试验中测试新的免疫检查点靶标。在晚期 CCA 和 GBC 中,PD-1 ICI 已导致抗肿瘤反应,但仅在少数选定患者中。其他 ICI 正在为 CCA 和 GBC 患者进行研究。过继转移可能有前途,转移性 CCA 报告完全持久消退,但这种治疗方法可能不可推广。已经开发了替代方法,并观察到有希望的结果,但需要临床试验来验证其效用。虽然肝胆癌的治疗涉及这些癌症带来的独特挑战,但 ICI 和过继转移的进展已将免疫疗法确立为这些具有挑战性的患者的重要治疗方法之一,这些患者几乎没有其他有效的治疗选择。
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