Targeting OLFM13 in colorectal cancer suppresses tumor growth and angiogenesis, and increases the efficacy of anti-PD1 based immunotherapy

Article Article scientifique Article Targeting OLFM13 in colorectal cancer suppresses tumor growth and angiogenesis, and increases the efficacy of anti-PD1 based immunotherapy eng 2021-09-15 2021-09-15 author Stalin Jimmy 0000-0001-8092-7057 844806 author Imhof Beat 0000-0002-6446-3990 114878 author Coquoz Oriana author Jeitziner Rachel author Hammel Philippe 541089 author Mckee Thomas Alexander 0000-0002-2147-3136 549937 author Jemelin Stéphane 116782 author Poittevin Marine 845371 author Pocard Marc author Matthes Thomas 27368 author Kaci Rachid author Delorenzi Mauro author Rüegg Curzio author Licina Marijana 0000-0001-9023-2208 133516 4625 10.3390/cancers13184625 34572851 2072-6694 PMC8464773 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. Blood vessel pericyte coverage Checkpoint inhibitors Colorectal cancer Tumor angiogenesis Tumor development Dewey 616 Dewey 616.07 Swiss National Science Foundation Neue matrizelluläre Moleküle beteiligt bei Angiogenese und vaskulären Erkrankungen 310030_153456 CH Project funding 56 Département de médecine 221 137 Département de pathologie et immunologie 21F false 586 Analyses cellulaires et moléculaires des hémopathies malignes 929 476 Lymphomes MALT et réplication virale 807 Cancers 13 18 4f72fe1b-c34d-40d3-b00d-61aa84a3138d Article (Published version) Public 34572851_BIB_64B45ACEAD1A.pdf 9326259 application/pdf CC BY-4.0 36a0ffb8-160b-44f3-a232-6a43d1aacf0a Appendix Public cancers-13-04625-s001.zip 954846 application/zip CC BY-4.0 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Targeting OLFM13 in colorectal cancer suppresses tumor growth and angiogenesis, and increases the efficacy of anti-PD1 based immunotherapy	Cancers			2021	201	254

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Stalin, Jimmy