Transcriptome Analysis of Tumor Associated High Endothelial Venules in Breast Cancer

High endothelial venules (HEVs) are specialized post-capillary venules that recruit naïve lymphocytes to the lymph nodes and are essential for the development of adaptive immunity. HEVs can also develop in tumors. These specialized tumor vessels are thought to be important for recruiting naïve T cells and B cells into tumors and locally enhancing anti-tumor immunity by supporting the formation of tertiary lymphoid structures. By a comparative transcriptome analysis in human breast cancer, we investigated differentially expressed genes between tumor-associated HEVs and the rest of the tumor vasculature. Tumor vessels highly expressing HEV-upregulated genes, such as the homeobox gene MEOX2 and the tetraspanin gene TSPAN7, were associated with extensive infiltration of T and B lymphocytes and the occurrence of tertiary lymphoid structures, which is known to predict therapeutic responses to immune checkpoint inhibitors. Moreover, high transcript counts of these genes in clinical tumor specimens were associated with a significant survival benefit in advanced breast cancer. The molecular signature of HEVs identified here may be useful for guiding immunotherapies and provide a new direction for investigating tumor-associated HEVs and their clinical significance. mRNA profiles of tumor vessels and high endothelial venules in TLS-rich and TLS-free breast tumors