Journal Article

DKFZ-2026-00509

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Harnessing lipid-driven immunometabolic pathways in omental metastases to enhance immunotherapy in patients with ovarian cancer.

Suarez-Carmona, M. (First author)DKFZ* ; Hampel, M.DKFZ* ; Zhang, X.-W.DKFZ* ; Pöchmann, A.DKFZ* ; Grauling-Halama, S. A.DKFZ* ; Valous, N. A.DKFZ* ; Charoentong, P.DKFZ* ; Ferber, D. ; Wissfeld, J. ; Höflich, A.DKFZ* ; Goriely, S. ; Detavernier, A. ; Azouz, A. ; Rongvaux, A. ; Zukunft, S. ; Fleming, I. ; Okun, J. G. ; Baracos, V. ; Heikenwalder, M.DKFZ* ; Zitvogel, L. ; Xu, X. ; Xu, C. ; Volkmar, M.DKFZ* ; Schraivogel, D. ; Steinmetz, L. ; Hamanishi, J. ; Mandai, M. ; Gaida, M. ; Mokry, T.DKFZ* ; Nattenmüller, J.DKFZ* ; Sedlaczek, O.DKFZ* ; Monje, N. ; Schwab, R. ; Hasenburg, A. ; Mavratzas, A. ; Boger, R. J. ; Marmé, F. ; Schott, S. ; Halama, N. (Last author)DKFZ*

2026
Macmillan Publishers, part of Springer Nature London

Abstract: Immunotherapy with immune checkpoint blockade (ICB) in epithelial ovarian carcinoma (EOC) shows limited clinical benefit only for a small subset of patients. Overall response rates are low, so that overcoming immunotherapy resistance and improved stratification are key. In this study, we investigated the immunometabolic landscape of EOC with a focus on omental metastases, identifying lipid-laden macrophages as central elements for actionable therapeutic vulnerabilities and giving rise to biomarkers for improved patient stratification. Using patient-derived explants, we demonstrated a functional dichotomy inside the typically lipid-rich microenvironment of omental metastases: augmented maintenance of effector T cell function, while lipid uptake and processing by tumor-associated macrophages (TAMs) induces oxidative stress-dependent signaling programs, which drive macrophage dysfunction and immune suppression. Pharmacological modulation of lipid-driven signaling pathways through CCR5 inhibition (inflammation modulation through maraviroc) or blockade of the lipid scavenger receptor CD36 reprograms TAMs, restores T cell activity, and enhances antitumor immune responses within lipid-rich tumor niches. Mechanistically, studies in humanized mouse models reveal that maraviroc-mediated CCR5 inhibition induces transcriptional programs associated with immune activation in stressed, lipid-laden human TAMs. Consistent with these mechanistic insights, we demonstrated that the specific immunometabolic niche in omental metastases is clinically associated with responsiveness to ICB. We propose a non-invasive radiomics and machine-learning-based analysis of imaging data to assess omental involvement for patient stratification.

Note: #EA:D196#LA:D196# / #DKTKZFB26# / #NCTZFB26#

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Contributing Institute(s):

1. Translationale Immuntherapie (D196)
2. Angewandte Tumor-Immunität (D120)
3. Chronische Entzündung und Krebs (D440)
4. HI-TRON zentral (D190)
5. E010 Radiologie (E010)
6. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2026

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Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 30 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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