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. 2023 May 4;18(2):568–581. doi: 10.1007/s12072-023-10537-6

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© The Author(s) 2023

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — HCC and CRLM peripheral blood (PB) Tregs are highly represented: HCC Tregs are the most active. a Phenotypic characterization of peripheral Tregs (CD4⁺CD25^hiFoxp3⁺ T cells/ total lymphocytes) in 33 HCC and 24 CRLM as compared to 15 HD (HCC vs HD, p < 0.001; CRLM vs HD, p < 0.01). (ai) naïve (CD25^hiFOXP3^lowCD45RA⁺), activated (CD25^hiFOXP3^hiCD45RA⁻), and not suppressive (CD25^hiFOXP3^lowCD45RA⁻) Tregs in HCC, CRLM, and HD peripheral blood: (activated Tregs: HCC vs HD, p < 0.001; CRLM vs HD, p < 0.01); (HD: activated vs naïve and not suppressive Tregs, p < 0.05); (HCC and CRLM: activated vs naïve Tregs p < 0.05). (aii) Tregs activation markers in HCC and CRLM compared to HD: CTLA-4, CXCR4, PD-1, and ENTPD1 (HCC vs HD, p < 0.001); ICOS (HCC vs HD, p < 0.05); CTLA-4, CXCR4, and ENTPD1 (CRLM vs HD, p < 0.05); PD1 (CRLM vs HD, p < 0.01). b Functional PB-derived Tregs from 24 HCC, 20 CRLM patients, and 15 HD by CFSE suppression assay (PB-HCC/CRLM vs PB-HD: p < 0.001; PB-HCC vs PB-CRLM: p < 0.01). c Peripheral M-MDSCs (CD14⁺HLA-DR^low/−CD15⁻) and PMN-MDSCs (CD11b⁺CD15⁺CD33⁺Lin⁻HLA-DR^low/−) in HCC and CRLM (M-MDSCs: HCC vs HD: p < 0.001; CRLM vs HD: p < 0.01; HCC vs CRLM: p < 0.05); (PMN-MDSCs: HCC vs HD, p < 0.01; HCC vs CRLM, p < 0.01). Peripheral CD8⁺ effector cells (CD8⁺CD45R4⁺CD62L.⁻) in HCC and CRLM (CRLM vs HD, P < 0.05; HCC vs CRLM, p < 0.05)