Faculty Collaboration Database

Perioperative poly(I:C) reverses accelerated tumor growth after surgery in neuroblastoma. Immunohorizons 2025 Nov 09;9(11)

Date

11/10/2025

Pubmed ID

41208108

Pubmed Central ID

PMC12597879

DOI

10.1093/immhor/vlaf058

Scopus ID

2-s2.0-105021199974 (requires institutional sign-in at Scopus site)

Abstract

Surgery for local control is a cornerstone of anticancer therapy with demonstrated survival benefit. However, surgery-induced modulation of antitumor immunity may also contribute to cancer progression and relapse. Despite evidence for a pro-tumor surgery effect in adult cancers, there remain significant knowledge gaps as to the influence surgery has on recurrence or metastatic outgrowth in pediatric cancers. High-risk neuroblastoma (HR-NB) is the most common extracranial solid tumor of childhood. While almost all children with HR-NB undergo surgery, nearly 50% suffer metastatic relapse and succumb to their disease. To ascertain if surgery may contribute to recurrence in HR-NB, we developed a mouse model to comprehensively interrogate the systemic effect of surgery on distant tumor growth and immune modulation. This model demonstrated that MYCN-amplified HR-NB tumor growth was accelerated by surgery compared to tumor-bearing mice without surgical stress. Accelerated tumor growth was absent in HR-NB cells engrafted to immune deficient mice, suggesting that an intact immune system may be needed for surgery to exert its pro-growth effect on distant tumor cells. Consistent with that genetic ablation model, flow cytometry measured a decrease in splenic macrophages (Mϕ) and dendritic cells (DC) and an increase in myeloid-derived suppressor cells (MDSC) after surgery. Perioperative treatment with polyinosinic-polycytidylic acid [poly(I:C)] ameliorated surgery-induced tumor growth. These findings provide direct insight into the systemic surgical effect on pediatric solid tumor growth and identify innate immune adjuvants as a potential perioperative treatment to mitigate this effect.

Author List

Mao C, Poimenidou M, McAllister D, Dwinell MB, Craig BT

Authors

Brian T. Craig MD Assistant Professor in the Surgery department at Medical College of Wisconsin
Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Chenkai Mao Research Scientist I in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Dendritic Cells
Disease Models, Animal
Female
Humans
Macrophages
Mice
N-Myc Proto-Oncogene Protein
Neuroblastoma
Poly I-C