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. 2021 May 20;9:37. doi: 10.1186/s40364-021-00290-z

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© The Author(s) 2021

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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — PD1 expression in CD8⁺ T cells after co-culture with B-HD cells or B-CLL cells and contribution of soluble factors to PD1 expression. a Percentages of PD1⁺ CD8⁺ T cells from progressing CLL patients after stimulation with anti-CD3 and anti-CD28 for 7 days (grey dots) and in presence of B-HD cells (yellow dots) or B-CLL cells at the time of progression (red dots) at the indicated T:B ratios (n = 10). b Percentages of PD1⁺CD8⁺ T cells from non-progressing CLL patients after stimulation with anti-CD3 and anti-CD28 for 7 days (grey dots) and in presence of B-HD cells (yellow dots) or B-CLL cells at asymptomatic follow-up (blue dots) at the indicated T:B ratios (n = 7). c Percentages of PD1⁺CD8⁺ T cells from age-matched healthy donors (T-HD) after stimulation with anti-CD3 and anti-CD28 for 7 days (grey dots) and in presence of B-CLL cells at progression (bold red dots) or B-CLL cells at asymptomatic follow-up (bold blue dots) at the indicated T:B ratios (n = 6). d Percentages of PD1⁺CD8⁺ T cells from CLL patients after stimulation with anti-CD3 and anti-CD28 for 7 days and in contact with B-CLL cells or separated by transwell inserts at 1:10 T:B ratio (n = 14). e Concentration (pg/ml) of IL-10 in plasma from progressing (left, n = 19) and non-progressing patients (middle, n = 10). Increment of IL-10 in plasma between time points comparing progressing and non-progressing patients (right). f Percentage of IL-10⁺ CLL cells in progressing (left, n = 7) and non-progressing patients (middle, n = 5) at the two time points after co-culture of paired PBMCs with bone marrow stromal UE6E7T-2 cells, CD40L and TLR9L for 48 h. Increment of IL-10⁺ CLL cells between time points in progressing and non-progressing patients (right). g Percentage of PD1⁺CD8⁺ T cells from CLL after 7-day co-culture with progressing B-CLL cells at 1:10 T:B ratio, following the protocol previously described, and after adding anti-human IL-10 neutralizing antibody (n = 11). Graphs show mean ± SEM or paired values (*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; Wilcoxon matched paired test or Mann-Whitney test)