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@article{Sprooten:2021:10.1136/jitc-2021-003609,
author = {Sprooten, J and Vankerckhoven, A and Vanmeerbeek, I and Borras, DM and Berckmans, Y and Wouters, R and Laureano, RS and Baert, T and Boon, L and Landolfo, C and Testa, AC and Fischerova, D and Van, Holsbeke C and Bourne, T and Chiappa, V and Froyman, W and Schols, D and Agostinis, P and Timmerman, D and Tejpar, S and Vergote, I and Coosemans, A and Garg, AD},
doi = {10.1136/jitc-2021-003609},
journal = {Journal for ImmunoTherapy of Cancer},
pages = {1--18},
title = {Peripherally-driven myeloid NFkB and IFN/ISG responses predict malignancy risk, survival, and immunotherapy regime in ovarian cancer},
url = {http://dx.doi.org/10.1136/jitc-2021-003609},
volume = {9},
year = {2021}
}

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TY  - JOUR
AB  - Background Tumors can influence peripheral immune macroenvironment, thereby creating opportunities for non-invasive serum/plasma immunobiomarkers for immunostratification and immunotherapy designing. However, current approaches for immunobiomarkers’ detection are largely quantitative, which is unreliable for assessing functional peripheral immunodynamics of patients with cancer. Hence, we aimed to design a functional biomarker modality for capturing peripheral immune signaling in patients with cancer for reliable immunostratification.Methods We used a data-driven in silico framework, integrating existing tumor/blood bulk-RNAseq or single-cell (sc)RNAseq datasets of patients with cancer, to inform the design of an innovative serum-screening modality, that is, serum-functional immunodynamic status (sFIS) assay. Next, we pursued proof-of-concept analyses via multiparametric serum profiling of patients with ovarian cancer (OV) with sFIS assay combined with Luminex (cytokines/soluble immune checkpoints), CA125-antigen detection, and whole-blood immune cell counts. Here, sFIS assay’s ability to determine survival benefit or malignancy risk was validated in a discovery (n=32) and/or validation (n=699) patient cohorts. Lastly, we used an orthotopic murine metastatic OV model, with anti-OV therapy selection via in silico drug–target screening and murine serum screening via sFIS assay, to assess suitable in vivo immunotherapy options.Results In silico data-driven framework predicted that peripheral immunodynamics of patients with cancer might be best captured via analyzing myeloid nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) signaling and interferon-stimulated genes' (ISG) responses. This helped in conceptualization of an ‘in sitro’ (in vitro+in situ) sFIS assay, where human myeloid cells were exposed to patients’ serum in vitro, to assess serum-induced (si)-NFκB or interferon (IFN)/ISG responses (as act
AU  - Sprooten,J
AU  - Vankerckhoven,A
AU  - Vanmeerbeek,I
AU  - Borras,DM
AU  - Berckmans,Y
AU  - Wouters,R
AU  - Laureano,RS
AU  - Baert,T
AU  - Boon,L
AU  - Landolfo,C
AU  - Testa,AC
AU  - Fischerova,D
AU  - Van,Holsbeke C
AU  - Bourne,T
AU  - Chiappa,V
AU  - Froyman,W
AU  - Schols,D
AU  - Agostinis,P
AU  - Timmerman,D
AU  - Tejpar,S
AU  - Vergote,I
AU  - Coosemans,A
AU  - Garg,AD
DO  - 10.1136/jitc-2021-003609
EP  - 18
PY  - 2021///
SN  - 2051-1426
SP  - 1
TI  - Peripherally-driven myeloid NFkB and IFN/ISG responses predict malignancy risk, survival, and immunotherapy regime in ovarian cancer
T2  - Journal for ImmunoTherapy of Cancer
UR  - http://dx.doi.org/10.1136/jitc-2021-003609
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000720981900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://jitc.bmj.com/content/9/11/e003609
UR  - http://hdl.handle.net/10044/1/93602
VL  - 9
ER  -

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