Host obesity alters the ovarian tumor immune microenvironment and impacts response to standard of care chemotherapy.
Fibrosis
High fat diet
Obesity
Ovarian cancer
Tumor-associated macrophage
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
12 Jul 2023
12 Jul 2023
Historique:
received:
11
04
2023
accepted:
25
06
2023
medline:
14
7
2023
pubmed:
13
7
2023
entrez:
12
7
2023
Statut:
epublish
Résumé
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). 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 37438818
doi: 10.1186/s13046-023-02740-y
pii: 10.1186/s13046-023-02740-y
pmc: PMC10337170
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
165Subventions
Organisme : NIH HHS
ID : F99/K00AG068527
Pays : United States
Organisme : NIH HHS
ID : UO1CA236979
Pays : United States
Organisme : NIA NIH HHS
ID : F99 AG068527
Pays : United States
Organisme : NIA NIH HHS
ID : K00 AG068527
Pays : United States
Organisme : NCI NIH HHS
ID : K01 CA218305
Pays : United States
Organisme : NCI NIH HHS
ID : RO1CA109545
Pays : United States
Organisme : NIH HHS
ID : KO1CA218305
Pays : United States
Informations de copyright
© 2023. The Author(s).
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