Microvascular endothelial cells PD-L1 expression predicts the efficacy and side effects of anlotinib

Yingfang Feng¹Yuan Gao¹Shaochuan Liu¹Tingting Qin¹Yan Zhang²Jing Wang¹Kai Li^1*

• ¹Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
• ²Tianjin Haihe Hospital, Tianjin, China

Immunotherapy plays a crucial role in tumors treatment. However, still few researches are performed on 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 cells 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 an increased infiltration of CD8 + T cells in the tissue. Additionally, the antitumor effect of anlotinib was most pronounced when administered during the mid-stage of the tumor.This study evaluated the most effective timing for anlotinib to downregulate PD-L1 expression in tumor and normal tissues so to promote immune infiltration in the tissues. Our findings can provide valuable references for the clinical use of anlotinib and to caution its side effects.