Feng Yingfang, Gao Yuan, Liu Shaochuan, Qin Tingting, Zhang Yan, Wang Jing, Li Kai
Department of Thoracic Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Front Oncol. 2025 Jul 30;15:1544278. doi: 10.3389/fonc.2025.1544278. eCollection 2025.
Immunotherapy plays a crucial role in the treatment of tumors. However, few studies have investigated the relationship between the expression of Programmed Cell Death Ligand 1 (PD-L1, CD274) in microvascular endothelial cells (MECs), including blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and immune cell infiltration within tissues.
In our study, we utilized data from The Cancer Genome Atlas, a mouse subcutaneous xenograft model, and immunofluorescence and immunohistochemical staining to investigate the relationship between PD-L1 expression in melanoma MECs at different tumor stages and the infiltration of CD8 T cells in tumor and normal organs, under conditions with and without anlotinib treatment.
We found that PD-L1 expression was upregulated in tumor MECs, while anlotinib downregulated PD-L1 expression in both tumor and normal tissue MECs, corresponding with increased infiltration of CD8 T cells in the tissues. Additionally, the antitumor effect of anlotinib was most pronounced when administered during the mid-stage of tumor development.
This study evaluated the most effective timing for anlotinib to downregulate PD-L1 expression in tumor and normal tissues to promote immune infiltration. Our findings may offer valuable insights for the clinical use of anlotinib and its potential side effects.
免疫疗法在肿瘤治疗中发挥着关键作用。然而，很少有研究调查包括血液内皮细胞（BECs）和淋巴管内皮细胞（LECs）在内的微血管内皮细胞（MECs）中程序性细胞死亡配体1（PD-L1，CD274）的表达与组织内免疫细胞浸润之间的关系。
在我们的研究中，我们利用来自癌症基因组图谱的数据、小鼠皮下异种移植模型以及免疫荧光和免疫组织化学染色，来研究在有和没有安罗替尼治疗的情况下，不同肿瘤阶段黑色素瘤MECs中PD-L1表达与肿瘤及正常器官中CD8 T细胞浸润之间的关系。
我们发现肿瘤MECs中PD-L1表达上调，而安罗替尼下调肿瘤和正常组织MECs中的PD-L1表达，这与组织中CD8 T细胞浸润增加相对应。此外，安罗替尼在肿瘤发展中期给药时的抗肿瘤作用最为明显。
本研究评估了安罗替尼下调肿瘤和正常组织中PD-L1表达以促进免疫浸润的最有效时机。我们的发现可能为安罗替尼的临床应用及其潜在副作用提供有价值的见解。
