2026-08-28T08:16:34Zhttps://gredos.usal.es/oai/request
oai:gredos.usal.es:10366/1552022025-04-30T20:45:40Zcom_10366_123989com_10366_4512com_10366_3823col_10366_123990
Gestión del Repositorio Documental de la Universidad de Salamanca author Landeira-Viñuela, Alicia author Arias-Hidalgo, Carlota author Juanes-Velasco, Pablo author Alcoceba Sánchez, Miguel author Navarro Bailón, Almudena author Pedreira, Carlos Eduardo author Lecrevisse, Quentin author Díaz Muñoz, Laura author Sánchez Santos, José Manuel author Hernández García, Ángela Patricia author García-Vaquero, Marina L. author Góngora Fernández, Rafael author Rivas Sanz, Javier de las author González, Marcos author Orfao de Matos Correia e Vale, José Alberto author Fuentes García, Manuel 2024-02-02T09:57:02Z 2024-02-02T09:57:02Z 2022 1664-3224 http://hdl.handle.net/10366/155202 1664-3224 [EN]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 (MBLhi)], 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 MBLhi) has been systematically evaluated. Also, differential profiles of soluble immune factors that discriminate between MBLhi 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. eng CC0 1.0 Universal cellular microenvironment chronic lymphocytic leukaemia (CLL) cytokines profiles immune dysfunction soluble immune checkpoints Unravelling soluble immune checkpoints in chronic lymphocytic leukemia: Physiological immunomodulators or immune dysfunction info:eu-repo/semantics/article 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 URL https://gredos.usal.es/bitstream/10366/155202/1/2022-Frontiers-ICs%20in%20CLL.pdf File MD5 fc9000129f4b6dcc31e87c0b52c0ec78 4797459 application/pdf 2022-Frontiers-ICs in CLL.pdf URL https://gredos.usal.es/bitstream/10366/155202/4/2022-Frontiers-ICs%20in%20CLL.pdf.txt File MD5 bbe060935413c367ff5b1d83c739e880 71947 text/plain 2022-Frontiers-ICs in CLL.pdf.txt