This preclinical study showed that CCR2/CCR5 dual-antagonist counteracts radiation-induced suppressive signals in myeloid cells and upregulates the effector T cell pathway and supported the ongoing clinical trial of the combination therapy of radiation, CCR2/CCR5 dual-antagonist, and anti–PD-1 antibody for locally advanced pancreatic cancer. Here, CCR2 is linked to pancreatic neoplasm.