Department of Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203 Berlin, Germany.
Department of Surgery, Park-Klinik Weißensee, 13086 Berlin, Germany.
Int J Mol Sci. 2023 Jan 21;24(3):2160. doi: 10.3390/ijms24032160.
Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively, < 0.05). For the presence of TIM3, IDO, B7H4, and LAG3, no difference in OS was observed ( > 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference ( = 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT.
免疫检查点疗法 (ICT) 在治疗多种实体肿瘤方面显示出了巨大的潜力。然而，ICT 在胰腺导管腺癌 (PDAC) 中的作用仍然有限。PDAC 中的免疫检查点 (IC) 模式为建立有效的 ICT 提供了基础。本研究旨在创建 PDAC 癌细胞中 IC 表达及其预后相关性的图谱。因此，使用免疫组织化学方法研究了 68 例经组织学证实的 PDAC 患者肿瘤切除后外周和中央组织微阵列 (TMA) 点的肿瘤细胞中 TIM3、IDO、B7H4、LAG3、VISTA 和 PD-L1 的表达情况，并将其与总生存期 (OS) 进行了比较。分别观察到 VISTA 和 PD-L1 的存在与较短的 OS 显著相关（中位 OS：22 个月与 7 个月和 22 个月与 11 个月，分别为 <0.05）。对于 TIM3、IDO、B7H4 和 LAG3 的存在，OS 没有差异（>0.05）。对 VISTA 和 PD-L1 的联合亚组的 OS 分析显示具有总体统计学意义差异（=0.02）。这些结果表明，VISTA 和 PD-L1 的存在具有预后相关性，并可能使其成为 ICT 的潜在靶点。
