University of Notre Dame
Browse
- No file added yet -

Host obesity alters the ovarian tumor immune microenvironment and impacts response to standard of care chemotherapy

journal contribution
posted on 2024-01-11, 20:25 authored by Yueying Liu, Jing Yang, Tyvette S. Hilliard, Zhikun Wang, Jeff JohnsonJeff Johnson, Wanrui Wang, Elizabeth I. Harper, Connor Ott, Caitlin O'Brien, Leigh Campbell, Brian Crowley, Stephen Grisoli, Nicholas M. Stavrou, Anna Juncker-Jensen, M. Sharon Stack

Background: The majority of women with epithelial ovarian cancer (OvCa) are diagnosed with metastatic disease, resulting in a poor 5-year survival of 31%. Obesity is a recognized non-infectious pandemic that increases OvCa incidence, enhances metastatic success and reduces survival. We have previously demonstrated a link between obesity and OvCa metastatic success in a diet-induced obesity mouse model wherein a significantly enhanced tumor burden was associated with a decreased M1/M2 tumor-associated macrophage ratio (Liu Y et al. Can, Res. 2015; 75:5046-57).

Methods: The objective of this study was to use pre-clinical murine models of diet-induced obesity to evaluate the effect of a high fat diet (HFD) on response to standard of care chemotherapy and to assess obesity-associated changes in the tumor microenvironment. Archived tumor tissues from ovarian cancer patients of defined body mass index (BMI) were also evaluated using multiplexed immunofluorescence analysis of immune markers.

Results: We observed a significantly diminished response to standard of care paclitaxel/carboplatin chemotherapy in HFD mice relative to low fat diet (LFD) controls. A corresponding decrease in the M1/M2 macrophage ratio and enhanced tumor fibrosis were observed both in murine DIO studies and in human tumors from women with BMI > 30.

Conclusions: Our data suggest that the reported negative impact of obesity on OvCa patient survival may be due in part to the effect of the altered M1/M2 tumor-associated macrophage ratio and enhanced fibrosis on chemosensitivity. These data demonstrate a contribution of host obesity to ovarian tumor progression and therapeutic response and support future combination strategies targeting macrophage polarization and/or fibrosis in the obese host.

History

Date Created

2023-07-12

Language

  • English

Publisher

J Exp Clin Cancer Res, 2023 Jul 12;42(1):165.

Usage metrics

    Integrated Imaging Facility

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC