We show that a subset of OPC tumors and tumor cell lines secrete IL-1α that drives elevated gene expression of PTGS2 (COX-2) by monocytes isolated from circulating PBMC, independent of alterations in PIK3CA. We also show that patient’s monocytes are hyper-responsive to stimulation by IL-1α present in conditioned media, and that control monocytes show hyper-responsiveness by combined PGE2 and IL-1α exposure. Here, PTGS2 is linked to neoplasm.