Universität zu Köln

Heath, Owen, Berlato, Chiara, Maniati, Eleni ORCID: 0000-0001-6993-9890, Lakhani, Anissa, Pegrum, Colin, Kotantaki, Panoraia, Elorbany, Samar, Bohm, Steffen, Barry, Simon T., Annibaldi, Alessandro, Barton, Desmond P. and Balkwill, Frances R. (2021). Chemotherapy Induces Tumor-Associated Macrophages that Aid Adaptive Immune Responses in Ovarian Cancer. Cancer Immunol. Res., 9 (6). S. 665 - 682. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 2326-6074

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Abstract

Neoadjuvant chemotherapy (NACT) may stimulate anticancer adaptive immune responses in high-grade serous ovarian cancer (HGSOC), but little is known about effects on innate immunity. Using omental biopsies from HGSOC, and omental tumors from orthotopic mouse HGSOC models that replicate the human tumor microenvironment, we studied the impact of platinum-based NACT on tumor-associated macrophages (TAM). We found that chemotherapy reduces markers associated with alternative macrophage activation while increasing expression of proinflammatory pathways, with evidence of inflammasome activation. Further evidence of a shift in TAM functions came from macrophage depletion via CSF1R inhibitors (CSF1Ri) in the mouse models. Although macrophage depletion in established disease had no impact on tumor weight or survival, CSF1Ri treatment after chemotherapy significantly decreased disease-free and overall survival. This decrease in survival was accompanied by significant inhibition of adaptive immune response pathways in the tumors. We conclude that chemotherapy skews the TAM population in HSGOC toward an antitumor phenotype that may aid adaptive immune responses, and therapies that enhance or sustain this during remission may delay relapse.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heath, Owen UNSPECIFIED UNSPECIFIED UNSPECIFIED Berlato, Chiara UNSPECIFIED UNSPECIFIED UNSPECIFIED Maniati, Eleni UNSPECIFIED orcid.org/0000-0001-6993-9890 UNSPECIFIED Lakhani, Anissa UNSPECIFIED UNSPECIFIED UNSPECIFIED Pegrum, Colin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kotantaki, Panoraia UNSPECIFIED UNSPECIFIED UNSPECIFIED Elorbany, Samar UNSPECIFIED UNSPECIFIED UNSPECIFIED Bohm, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Barry, Simon T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Annibaldi, Alessandro UNSPECIFIED UNSPECIFIED UNSPECIFIED Barton, Desmond P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Balkwill, Frances R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-582145
DOI:	10.1158/2326-6066.CIR-20-0968
Journal or Publication Title:	Cancer Immunol. Res.
Volume:	9
Number:	6
Page Range:	S. 665 - 682
Date:	2021
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	2326-6074
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEOADJUVANT CHEMOTHERAPY; MICROENVIRONMENT Multiple languages Oncology; Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58214