Gene expression profiling of H16sc-IS1, Control H16sc-ImP and ILs-OE H16sc-ImP cancer cells.

It is well established that symptomatic cancers evade immune destruction by coalescing lesional and tumor microenvironments to suppress adaptive immunity. Additionally, mouse models of cervical and other cancers have revealed a capability of tumors to systemically induce the expansion of myeloid cells that cripple T cell development in spleen and lymph nodes, further impairing immune responses. We show that HPV16-driven cervical cancers release into the circulatory system four immunoregulatory ligands – IL1a, IL1ß, IL33, and IL36ß – that bias the bone marrow toward granulocytic myelopoiesis, producing immunosuppressive neutrophils and myeloid progenitors differentially populating spleens and tumors to facilitate immune evasion. A pan-IL1 receptor antagonist, anti-IL1RAP, attenuates this myeloid expansion and complements an HPV-E7 peptide vaccine plus anti-CTLA4 to elicit anti-tumor immunity. Evidence for similar systemic activity of these four IL1 ligands in human cervical and other cancers encourages multi-targeting this signaling axis to broaden the scope of cancer immunotherapy. Overall design: Comparative gene expression profiling of H16sc-IS1, Imp cells with ILs-OE and Imp controls.