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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The interactions between T-cell chronic lymphoproliferative disorder (T-CLPD) tumor cells and the bystander immune cells may play a critical role in the failure of immune surveillance and disease progression, but the altered blood immune profiles of T-CLPD remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here we analyzed the distribution of residual non-tumoral immune cells in blood of 47 T-CLPD patients -14 T-prolymphocytic leukemia (T-PLL), 7 S\u00e9zary syndrome\/mycosis fungoides (SS\/MF) and 26 T-large granular lymphocytic leukemia (T-LGLL)-, as tumor models of neoplastic T-cells that resemble naive\/central memory (N\/CM), memory and terminal effector T-cells, respectively, compared to 110 age- and sex-matched healthy donors, using spectral flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, our results showed deeply altered immune cell profiles in T-PLL, characterized by significantly increased counts of monocytes, dendritic cells, B-cells, NK-cells and innate lymphoid cells (ILC) -particularly ILC3-, together with reduced normal T-cells. In contrast, SS\/MF showed neutrophilia, associated with decreased numbers of dendritic cells and NK-cells, potentially reflecting their increased migration from blood to the skin. In turn, T-LGLL displayed the mildest immune impairment, dependent on the TCD4+ <jats:italic>vs<\/jats:italic>. TCD8+ nature of the clonal T-cells and presence of <jats:italic>STAT3<\/jats:italic> mutations among T\u03b1\u03b2CD8+ T-LGLL cases. Further dissection of the normal T-cell compartment showed a significant reduction of the earliest T-cell maturation compartments (N\/CM) in T-PLL and SS\/MF, whereas T-cells remained within normal ranges in T-LGLL, with only a minor reduction of N\/CM T-cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings point out the existence of differentially altered innate\u00a0and adaptive immune cell profiles in the distinct diagnostic subtypes of T-CLPD, with progressively less pronounced alterations from T-PLL and SS\/MF to\u00a0T-LGLL.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1561152","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T09:42:53Z","timestamp":1742550173000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered immune cell profiles in blood of mature\/peripheral T-cell leukemia\/lymphoma patients: an EuroFlow study"],"prefix":"10.3389","volume":"16","author":[{"given":"F. 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