Unravelling soluble immune checkpoints in chronic lymphocytic leukemia: Physiological immunomodulators or immune dysfunction.

Autor:	Landeira-Viñuela A; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Arias-Hidalgo C; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Juanes-Velasco P; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Alcoceba M; Department of Hematology, University Hospital of Salamanca, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00233, Center Research-Centre Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC) Consejo Superior de Investigaciones Científicas - Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (CSIC-USAL, IBSAL), Salamanca, Spain., Navarro-Bailón A; Department of Hematology, University Hospital of Salamanca, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00233, Center Research-Centre Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC) Consejo Superior de Investigaciones Científicas - Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (CSIC-USAL, IBSAL), Salamanca, Spain., Pedreira CE; Systems and Computing Department Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia-Programa de Engenharia de Sistemas e Computação (COPPE-PESC), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Lecrevisse Q; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Díaz-Muñoz L; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Sánchez-Santos JM; Statistics Department, University of Salamanca, Salamanca, Spain., Hernández ÁP; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Department of Pharmaceutical Sciences, Organic Chemistry Section, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain., García-Vaquero ML; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Góngora R; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., De Las Rivas J; Bioinformatics and Functional Genomics Group, Cancer Research Center Instituto Universitario de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca (CIC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain., González M; Department of Hematology, University Hospital of Salamanca, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00233, Center Research-Centre Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC) Consejo Superior de Investigaciones Científicas - Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (CSIC-USAL, IBSAL), Salamanca, Spain., Orfao A; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Fuentes M; Department of Medicine and General Service of Cytometry, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)- CB16/12/00400, Cancer Research Centre-Instituto Universitario de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas - Universidad de Salamanca (CSIC-USAL), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Proteomics Unit, Cancer Research Centre-IBMCC, Instituto de Investigación Biomédica de Salamanca (IBSAL), University of Salamanca-Consejo Superior de Investigaciones Científicas (CSIC), Salamanca, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 28; Vol. 13, pp. 965905. Date of Electronic Publication: 2022 Sep 28 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.965905
Abstrakt:	Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasm characterized by the accumulation of mature B cells. The diagnosis is established by the detection of monoclonal B lymphocytes in peripheral blood, even in early stages [monoclonal B-cell lymphocytosis (MBL hi )], and its clinical course is highly heterogeneous. In fact, there are well-characterized multiple prognostic factors that are also related to the observed genetic heterogenicity, such as immunoglobulin heavy chain variable region (IGHV) mutational status, del17p, and TP53 mutations, among others. Moreover, a dysregulation of the immune system (innate and adaptive immunity) has been observed in CLL patients, with strong impact on immune surveillance and consequently on the onset, evolution, and therapy response. In addition, the tumor microenvironment is highly complex and heterogeneous (i.e., matrix, fibroblast, endothelial cells, and immune cells), playing a critical role in the evolution of CLL. In this study, a quantitative profile of 103 proteins (cytokines, chemokines, growth/regulatory factors, immune checkpoints, and soluble receptors) in 67 serum samples (57 CLL and 10 MBL hi ) has been systematically evaluated. Also, differential profiles of soluble immune factors that discriminate between MBL hi and CLL (sCD47, sCD27, sTIMD-4, sIL-2R, and sULBP-1), disease progression (sCD48, sCD27, sArginase-1, sLAG-3, IL-4, and sIL-2R), or among profiles correlated with other prognostic factors, such as IGHV mutational status (CXCL11/I-TAC, CXCL10/IP-10, sHEVM, and sLAG-3), were deciphered. These results pave the way to explore the role of soluble immune checkpoints as a promising source of biomarkers in CLL, to provide novel insights into the immune suppression process and/or dysfunction, mostly on T cells, in combination with cellular balance disruption and microenvironment polarization leading to tumor escape. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Landeira-Viñuela, Arias-Hidalgo, Juanes-Velasco, Alcoceba, Navarro-Bailón, Pedreira, Lecrevisse, Díaz-Muñoz, Sánchez-Santos, Hernández, García-Vaquero, Góngora, De Las Rivas, González, Orfao and Fuentes.)
Databáze:	MEDLINE
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