Network-based screening identifies sitagliptin as an antitumor drug targeting dendritic cells

Dendritic cell (DC)-mediated antigen presentation is essential for the priming and activation of tumor-specific T cells. However, few drugs that specifically manipulate DC functions are available. Here, we observed that DCs initiated a distinct transcriptional program during antigen presentation. We utilized a network-based approach to screen for DC-targeting therapeutics. Sitagliptin, an oral gliptin widely used for type 2 diabetes, was identified as a drug that targets DCs. In mouse models, sitagliptin inhibited tumor growth by enhancing DC-mediated antigen presentation, leading to better T cell activation. Overall design: cDC1 and cDC2 cells were isolated from MC38-EGFP tumor tissues by FACS. Cells were further divided into EGFP- and EGFP+ based on their EGFP signals. RNAseq was performed.