Kim Ryul, Park Joo Kyung, Kwon Minsuk, An Minae, Hong Jung Yong, Park Joon Oh, Lim Sung Hee, Kim Seung Tae
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oncol Res. 2024 Dec 20;33(1):57-65. doi: 10.32604/or.2024.049054. eCollection 2025.
Immune checkpoint inhibitors (ICIs) are effective in a subset of patients with metastatic solid tumors. However, the patients who would benefit most from ICIs in biliary tract cancer (BTC) are still controversial.
We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.
All patients had microsatellite stable (MSS) type tumors. Three of the 32 patients achieved partial response (PR), with an objective response rate (ORR) of 9.4% (95% confidence interval [CI], 2.0-25.2) and nine showed stable disease (SD), exhibiting a disease control rate (DCR) of 37.5% (95% CI, 21.1-56.3). For the 31 patients who had access to PD-1 ligand 1 (PD-L1) combined positive score (CPS) testing (cut-off value ≥1%), the ORR was not different between those who had PD-L1-positive (PD-L1+; 1/11, 9.1%) and PDL1-(2/20, 10.0%) tumors ( = 1.000). The tumor mutational burden (TMB) of PD-L1+ BTC was comparable to that of PD-L1-BTC ( = 0.630). TMB and any exonic somatic mutations were also not predictive of pembrolizumab response. Molecular analysis of blood and tumor samples demonstrated a relatively high natural killer (NK) cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor response. Moreover, the tumors of these patients presented high enrichment scores for NK cells, antitumor cytokines, and Th1 signatures, and a low enrichment score for cancer-associated fibroblasts.
This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.
免疫检查点抑制剂（ICI）在一部分转移性实体瘤患者中有效。然而，在胆管癌（BTC）中最能从ICI中获益的患者仍存在争议。
我们对32例接受ICI帕博利珠单抗二线治疗的转移性BTC患者的组织和血液进行了分子特征分析。
所有患者均为微卫星稳定（MSS）型肿瘤。32例患者中有3例达到部分缓解（PR），客观缓解率（ORR）为9.4%（95%置信区间[CI]，2.0 - 25.2），9例疾病稳定（SD），疾病控制率（DCR）为37.5%（95%CI，21.1 - 56.3）。对于31例可进行程序性死亡受体1配体1（PD-L1）联合阳性评分（CPS）检测（临界值≥1%）的患者，PD-L1阳性（PD-L1+；1/11，9.1%）和PD-L1阴性（2/20，10.0%）肿瘤患者的ORR无差异（P = 1.000）。PD-L1+ BTC的肿瘤突变负荷（TMB）与PD-L1- BTC相当（P = 0.630）。TMB和任何外显子体细胞突变也不能预测帕博利珠单抗的反应。对血液和肿瘤样本的分子分析显示，在实现肿瘤反应的患者中，帕博利珠单抗治疗前外周血中自然杀伤（NK）细胞比例相对较高。此外，这些患者的肿瘤表现出NK细胞、抗肿瘤细胞因子和Th1特征的高富集分数，以及癌症相关成纤维细胞的低富集分数。
本研究显示了与帕博利珠单抗在MSS型BTC中疗效相关的分子特征。
