HPV16-Expressing Tumors Release Multiple IL1 Ligands to Orchestrate Systemic Immunosuppression Whose Disruption Enables Efficacy of a Therapeutic Vaccine.

ABSTRACT: It is well-established that symptomatic cancers evade immune destruction by coalescing 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 neutrophils that cripple T-cell development in spleen and lymph nodes, further impairing immune responses. Now we show that human papillomavirus type 16 (HPV16)-driven squamous cell tumors in the cervix and skin release into the circulatory system four immunoregulatory ligands - IL-1α, IL-1β, IL-33, and IL-36β - that bias the bone marrow toward granulocytic myelopoiesis, producing immunosuppressive neutrophils populating spleens and tumors. An IL-1 family coreceptor antagonist, anti-IL1RAP, abrogates this neutrophil ex

SUBMITTER: Lecointre M 

PROVIDER: S-EPMC12223509 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature