Targeting OLFML3 in Colorectal Cancer Suppresses Tumor Growth and Angiogenesis, and Increases the Efficacy of Anti-PD1 Based Immunotherapy.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_64B45ACEAD1A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeting OLFML3 in Colorectal Cancer Suppresses Tumor Growth and Angiogenesis, and Increases the Efficacy of Anti-PD1 Based Immunotherapy.
Journal
Cancers
Author(s)
Stalin J., Imhof B.A., Coquoz O., Jeitziner R., Hammel P., McKee T.A., Jemelin S., Poittevin M., Pocard M., Matthes T., Kaci R., Delorenzi M., Rüegg C., Miljkovic-Licina M.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
15/09/2021
Peer-reviewed
Oui
Volume
13
Number
18
Pages
4625
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The role of the proangiogenic factor olfactomedin-like 3 (OLFML3) in cancer is unclear. To characterize OLFML3 expression in human cancer and its role during tumor development, we undertook tissue expression studies, gene expression analyses of patient tumor samples, in vivo studies in mouse cancer models, and in vitro coculture experiments. OLFML3 was expressed at high levels, mainly in blood vessels, in multiple human cancers. We focused on colorectal cancer (CRC), as elevated expression of OLFML3 mRNA correlated with shorter relapse-free survival, higher tumor grade, and angiogenic microsatellite stable consensus molecular subtype 4 (CMS4). Treatment of multiple in vivo tumor models with OLFML3-blocking antibodies and deletion of the Olfml3 gene from mice decreased lymphangiogenesis, pericyte coverage, and tumor growth. Antibody-mediated blockade of OLFML3 and deletion of host Olfml3 decreased the recruitment of tumor-promoting tumor-associated macrophages and increased infiltration of the tumor microenvironment by NKT cells. Importantly, targeting OLFML3 increased the antitumor efficacy of anti-PD-1 checkpoint inhibitor therapy. Taken together, the results demonstrate that OLFML3 is a promising candidate therapeutic target for CRC.
Keywords
blood vessel pericyte coverage, checkpoint inhibitors, colorectal cancer, tumor angiogenesis, tumor development
Pubmed
Web of science
Open Access
Yes
Create date
04/10/2021 10:23
Last modification date
12/01/2022 7:10
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