Inflammatory and subtype-dependent serum protein signatures predict survival beyond the ctDNA in aggressive B cell lymphomas.

Autor:	Arffman M; Research Programs Unit, Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Meriranta L; Research Programs Unit, Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Autio M; Research Programs Unit, Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Holte H; Department of Oncology, Oslo University Hospital and KG Jebsen Centre for B Cell Malignancies, Oslo, Norway., Jørgensen J; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark., Brown P; Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Jyrkkiö S; Department of Oncology, Turku University Hospital, Turku, Finland., Jerkeman M; Department of Oncology, Skane University Hospital, Lund, Sweden., Drott K; Department of Oncology, Skane University Hospital, Lund, Sweden., Fluge Ø; Department of Oncology, Haukeland University Hospital, Bergen, Norway., Björkholm M; Department of Medicine, Karolinska University Hospital, Stockholm, Sweden., Karjalainen-Lindsberg ML; Department of Pathology, Helsinki University Hospital, Helsinki, Finland., Beiske K; Department of Pathology, Oslo University Hospital, Oslo, Norway., Pedersen MØ; Department of Pathology, Zealand University Hospital, Roskilde, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Leivonen SK; Research Programs Unit, Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland., Leppä S; Research Programs Unit, Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland. Electronic address: sirpa.leppa@helsinki.fi.
Jazyk:	angličtina
Zdroj:	Med (New York, N.Y.) [Med] 2024 Jun 14; Vol. 5 (6), pp. 583-602.e5. Date of Electronic Publication: 2024 Apr 04.
DOI:	10.1016/j.medj.2024.03.007
Abstrakt:	Background: Biological heterogeneity of large B cell lymphomas (LBCLs) is poorly captured by current prognostic tools, hampering optimal treatment decisions. Methods: We dissected the levels of 1,463 serum proteins in a uniformly treated trial cohort of 109 patients with high-risk primary LBCL (ClinicalTrials.gov: NCT01325194) and correlated the profiles with molecular data from tumor tissue and circulating tumor DNA (ctDNA) together with clinical data. Findings: We discovered clinically and biologically relevant associations beyond established clinical estimates and ctDNA. We identified an inflamed serum protein profile, which reflected host response to lymphoma, associated with inflamed and exhausted tumor microenvironment features and high ctDNA burden, and translated to poor outcome. We composed an inflammation score based on the identified inflammatory proteins and used the score to predict survival in an independent LBCL trial cohort (ClinicalTrials.gov: NCT03293173). Furthermore, joint analyses with ctDNA uncovered multiple serum proteins that correlate with tumor burden. We found that SERPINA9, TACI, and TARC complement minimally invasive subtype profiling and that TACI and TARC can be used to evaluate treatment response in a subtype-dependent manner in the liquid biopsy. Conclusions: Altogether, we discovered distinct serum protein landscapes that dissect the heterogeneity of LBCLs and provide agile, minimally invasive tools for precision oncology. Funding: This research was funded by grants from the Research Council of Finland, Finnish Cancer Organizations, Sigrid Juselius Foundation, University of Helsinki, iCAN Digital Precision Cancer Medicine Flagship, Orion Research Foundation sr, and Helsinki University Hospital. Competing Interests: Declaration of interests H.H. (all outside of the submitted work): Genmab: honoraria, safety committee; Gilead: honoraria, advisory board; Incyte: honoraria, advisory board; Nordic Nanovector: honoraria, safety committee; Novartis: honoraria, advisory board; Takeda: honoraria, advisory board. J.J. (all outside of the submitted work): BMS: consultancy; Gilead: consultancy; Incyte: consultancy; Novartis: consultancy; Orion Pharma: consultancy; Roche: consultancy. M.B. (all outside of the submitted work): Astra Zeneca: consultancy; BMS/Celgene: consultancy; Incyte: consultancy; Janssen: consultancy; Mundipharma: consultancy; Nanexa: consultancy; Pfizer: consultancy; Roche: consultancy; Schain Research: consultancy; WntResearch: consultancy. M.J. (all outside of the submitted work): Abbvie: honoraria, research funding; Astra Zeneca: honoraria, research funding; BMS: honoraria, research funding; Genmab: honoraria; Incyte: honoraria; Janssen: honoraria, research funding; Kite/Gilead: consultancy, honoraria, research funding; Novartis: honoraria; Orion: honoraria; Roche: honoraria, research funding. S.L. (all outside of the submitted work): Genmab: consultancy, research funding; Gilead: consultancy; Incyte: consultancy; Nordic Nanovector: research funding; Novartis: consultancy, honoraria, research funding; Roche: consultancy, research funding; Merck: consultancy; Bayer: research funding; Celgene: consultancy, research funding; Orion: consultancy. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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