Atypical chemokine receptors: emerging therapeutic targets in cancer

Atypical chemokine receptors (ACKRs) regulate the availability of chemokines via chemokine scavenging, while also having the capacity to elicit downstream function through beta-arrestin coupling. This contrasts with conventional chemokine receptors that directly elicit immune cell migration through G protein-coupled signaling. The significance of ACKRs in cancer biology has previously been poorly understood, but recent findings have highlighted the multifaceted role of these receptors in tumorigenesis and immune response modulation within the tumor mi-croenvironment (TME). Additionally, recent research has expanded our understand-ing of the function of several receptors including GPR182, CCRL2, GPR1, PITPNM3, and C5aR2 that share similarities with the ACKR family. In this review, we discuss these recent developments, and highlight the opportunities and challenges of phar-macologically targeting ACKRs in cancer.