Department of Respiratory Medicine, Osaka City University, Graduate School of Medicine, Osaka, Japan.
Department of Clinical Oncology, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan.
Cancer Sci. 2022 Sep;113(9):3148-3160. doi: 10.1111/cas.15464. Epub 2022 Jul 18.
It is unclear whether tumor vascular endothelial growth factor receptor 2 expression affects the therapeutic efficacy of immune-checkpoint inhibitors and antiangiogenic agents. This retrospective, multicenter study included patients with advanced non-small cell lung cancer who were treated with immune-checkpoint inhibitors. We constructed tissue microarrays and performed immunohistochemistry with an anti-vascular endothelial growth factor receptor 2 antibody. We analyzed immune and tumor cell staining separately in order to determine their correlation with the objective response rate, progression-free survival, and overall survival in patients receiving immune-checkpoint inhibitors. Of 364 patients, 37 (10%) expressed vascular endothelial growth factor receptor 2 in immune cells and 165 (45%) in tumor cells. The objective response rate, progression-free survival, and overall survival were significantly worse in patients treated with immune checkpoint inhibitor monotherapy who expressed vascular endothelial growth factor receptor 2 in immune cells than those who did not (10% vs 30%, p = 0.028; median = 2.2 vs 3.6 months, p = 0.012; median = 7.9 vs 17.0 months, p = 0.049, respectively), while there was no significant difference based on tumor cell expression (24% vs 30%, p = 0.33; median = 3.1 vs 3.5 months, p = 0.55; median = 13.6 vs 16.8 months, p = 0.31). There was no significant difference in overall survival between patients treated with and without antiangiogenic agents in any treatment period based on vascular endothelial growth factor receptor 2 expression. Immune checkpoint inhibitor efficacy was limited in patients expressing vascular endothelial growth factor receptor 2 in immune cells.
肿瘤血管内皮生长因子受体 2 表达是否影响免疫检查点抑制剂和抗血管生成药物的治疗效果尚不清楚。本回顾性多中心研究纳入了接受免疫检查点抑制剂治疗的晚期非小细胞肺癌患者。我们构建了组织微阵列，并使用抗血管内皮生长因子受体 2 抗体进行了免疫组织化学染色。我们分别分析了免疫细胞和肿瘤细胞的染色情况，以确定它们与接受免疫检查点抑制剂治疗的患者的客观缓解率、无进展生存期和总生存期的相关性。在 364 例患者中，37 例（10%）的免疫细胞中表达血管内皮生长因子受体 2，165 例（45%）的肿瘤细胞中表达血管内皮生长因子受体 2。与未表达血管内皮生长因子受体 2 的患者相比，接受免疫检查点抑制剂单药治疗的表达血管内皮生长因子受体 2 的患者的客观缓解率、无进展生存期和总生存期明显更差（10% vs 30%，p=0.028；中位数=2.2 与 3.6 个月，p=0.012；中位数=7.9 与 17.0 个月，p=0.049），而基于肿瘤细胞表达的患者则无显著差异（24% vs 30%，p=0.33；中位数=3.1 与 3.5 个月，p=0.55；中位数=13.6 与 16.8 个月，p=0.31）。根据血管内皮生长因子受体 2 的表达，在任何治疗期间，接受和未接受抗血管生成药物治疗的患者的总生存期均无显著差异。在表达血管内皮生长因子受体 2 的免疫细胞中，免疫检查点抑制剂的疗效受到限制。
