No abstract

Colorectal adenocarcinoma is a leading cause of death worldwide, and immune infiltration in colorectal tumors has been recognized recently as an important pathophysiological event. In this context, tumor-associated macrophages (TAM) have been related to chemoresistance to 5fluorouracil (5-FU), the first-line chemotherapeutic agent used in treating colorectal cancers.Nevertheless, the details of this chemoresistance mechanism are still poorly elucidated. In the present study, we report that macrophages specifically overexpress dihydropyrimidine dehydrogenase (DPD) in hypoxia, leading to macrophage-induced chemoresistance to 5-FU via inactivation of the drug. Hypoxia-induced macrophage DPD expression was controlled by HIF-2α.