化疗和免疫疗法相结合治疗转移性胆管癌（CCA）比传统疗法有望提高生存率和缓解率。 TOPAZ-1 和 KEYNOTE-966 已经证明了免疫疗法（durvalumab 和 pembrolizumab）与化疗相结合的疗效，即使在胆囊癌 (GBC) 中也是如此，在 TOPAZ-1 试验中完全缓解率为 2.7%。采用免疫疗法组合治疗的晚期 CCA 已显示出受程序性死亡配体 1 (PD-L1) 或 Epstein-Barr 病毒高表达影响的完全缓解。通过将放疗与程序性细胞死亡蛋白 1 (PD-1) 阻断相结合，可以增强这些反应。一名 62 岁男性被诊断患有无法切除的 GBC、远处淋巴转移以及肝段 4i 和 5、结肠肝曲、十二指肠球和胰头的局部侵犯。免疫组织化学检查显示低分化鳞状细胞癌，不表达PD-L1。下一代测序揭示了 ERBB2 R678Q 的突变和微卫星稳定肿瘤。该患者于 2022 年 6 月开始接受顺铂-吉西他滨加 durvalumab 化疗免疫治疗。八个周期后，报告肿瘤体积和标志物显着减少，durvalumab 治疗一直维持到 2023 年 11 月。随后的计算机断层扫描显示，肿瘤体积和标志物显着减少。随后的计算机断层扫描显示，肿瘤体积和标志物显着减少。肿瘤体积，并进行手术切除。组织学检查证实不存在残留肿瘤或淋巴结转移。截至2024年6月，患者尚未出现疾病复发的迹象。目前已有几份关于 GBC 转化手术的报告，但术前化疗免疫治疗的数据有限。此外，CCA 和 GBC 中未经病理证实的完全缓解引发了关于免疫治疗后是否需要手术的几个问题。尽管已报道联合使用抗细胞毒性 T 淋巴细胞相关蛋白 4 和抗 PD-1 药物以及化疗可有效控制晚期 GBC 并促进肿瘤消退，但由于与 PD-1 的关联尚不明确，因此还需要进一步研究来确定可靠的预测生物标志物。 L1 表达或肿瘤突变负荷。总体而言，化学免疫疗法可有效治疗转移性 CCA，特别是针对特定分子谱进行定制时。这些治疗可能会带来完全的缓解和新颖的策略。版权所有：© Orlandi 等人。

The combination of chemotherapy and immunotherapy for metastatic cholangiocarcinoma (CCA) offers promising improvements in survival and response rates beyond traditional treatments. TOPAZ-1 and KEYNOTE-966 have demonstrated the efficacy of combining immunotherapy (durvalumab and pembrolizumab) with chemotherapy, even in gallbladder cancer (GBC), with a complete response rate of 2.7% in the TOPAZ-1 trial. Advanced CCA treated with immunotherapy combinations has shown complete responses influenced by high programmed death-ligand 1 (PD-L1) or Epstein-Barr virus expression. These responses were enhanced by combining radiotherapy with programmed cell death protein 1 (PD-1) blockade. A 62-year-old man was diagnosed with unresectable GBC, distant lymphatic metastases, and local invasion of liver segments 4i and 5, the colonic hepatic flexure, the duodenal bulb, and the pancreatic head. Immunohistochemical examination revealed poorly differentiated squamous cell carcinoma, without expression of PD-L1. Next generation sequencing revealed the mutation of ERBB2 R678Q and a microsatellite stable tumour. The patient started chemo-immunotherapy with cisplatin-gemcitabine plus durvalumab in June 2022. After eight cycles, a significant reduction in tumour volume and markers was reported, and therapy with durvalumab was maintained through November 2023. The subsequent computed tomography scans showed further reduction in the tumour volume, and surgical resection was performed. Histological examinations confirmed the absence of residual tumour or lymph node metastases. As of June 2024, the patient has shown no signs of disease recurrence. Several reports of conversion surgery in GBC exist, but data on pre-surgical chemo-immunotherapy are limited. Furthermore, a complete response without pathological confirmation in CCA and GBC raises several questions regarding the need for surgery after immunotherapy. Although effective disease control and tumour regression have been reported in advanced GBC with combined anti-cytotoxic T-lymphocyte associated protein 4 and anti-PD-1 agents and chemotherapy, further studies are needed to identify reliable predictive biomarkers due to unclear associations with PD-L1 expression or tumour mutational burden. Overall, chemo-immunotherapy has been effective in treating metastatic CCA, especially when tailored to specific molecular profiles. These treatments may lead to complete responses and novel strategies.Copyright: © Orlandi et al.