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Abstract：
Immune checkpoint inhibitors (ICIs) have shown promising efficacy in multiple cancers including biliary tract cancers (BTCs). However, the data focusing on the efficacy of ICIs in patients with gallbladder cancer (GBC) is still limited. In this study, we aim to assess the efficacy of ICIs in GBC and explore the clinicopathologic and molecular markers associated with ICI benefit. We retrospective analyzed 69 GBC patients who had received ICI therapy between January 2016 and December 2020. Tumor samples were obtained for genomic sequencing and immunohistochemical analysis. The median progression-free survival (PFS) and overall survival (OS) was 4.4 months and 8.5 months, respectively. Multivariate analysis indicated that alcohol intake history, carcinoma embryonic antigen (CEA) level ≥100 U/mL, and cutaneous immune-related adverse events (irAEs) were independent prognostic factors for PFS. CEA level ≥100 U/mL and cutaneous irAEs were independent prognostic factors for OS. The objective response rate and disease control rate (DCR) were 15.9% and 37.7%, respectively. Patients with cutaneous irAEs, high CD8+ T cell infiltrated or immune inflamed GBCs had higher DCR. Patients with high CD8+ T cell infiltrated or immune inflamed GBCs also had a notably improved prognosis. These results suggest that ICIs were effective in patients with GBC. High CEA level, cutaneous irAEs, high CD8+ T cell infiltration, and immune inflamed phenotype could be useful for predicting the efficacy of ICIs in GBC.
摘要：
免疫检查点抑制剂(ICIs)已在包括胆道癌(BTC)在内的多种癌症中显示出有希望的功效。然而,关于ICIs在胆囊癌(GBC)患者中的疗效的数据仍然有限.在这项研究中,我们旨在评估ICI在GBC中的疗效,并探讨与ICI获益相关的临床病理和分子标志物.我们回顾性分析了在2016年1月至2020年12月期间接受ICI治疗的69例GBC患者。获得肿瘤样品用于基因组测序和免疫组织化学分析。中位无进展生存期(PFS)和总生存期(OS)分别为4.4个月和8.5个月,分别。多因素分析表明，饮酒史，癌胚抗原(CEA)水平≥100U/mL,皮肤免疫相关不良事件（irAEs）是影响PFS的独立预后因素。CEA水平≥100U/mL和皮肤irAE是OS的独立预后因素。客观有效率和疾病控制率(DCR)分别为15.9%和37.7%,分别。皮肤irAE患者，高CD8+T细胞浸润或免疫发炎的GBCs有较高的DCR。具有高CD8+T细胞浸润或免疫发炎的GBCs的患者也具有显著改善的预后。这些结果表明ICI对GBC患者有效。高CEA水平,皮肤iRAE，高CD8+T细胞浸润，免疫炎症表型可用于预测ICIs在GBC中的疗效。
