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. 2024 Nov 1;109(11):3760-3765.
doi: 10.3324/haematol.2024.285170.

Response to DA-EPOCH-R is associated with activation of 'fitter' cytotoxic T cells in patients with newly diagnosed double and triple hit high-grade B-cell lymphoma

A Vera De Jonge  1 , Wassilis S C Bruins  1 , Carolien Duetz  1 , Charlotte L B M Korst  1 , Rosa Rentenaar  1 , Meliha Cosovic  1 , Merve Eken  1 , Marie-Jose Kersten  1 , Yorick Sandberg  2 , Rozemarijn S Van Rijn  3 , Rob Fijnheer  4 , Pim Mutsaers  5 , Vibeke K J Vergote  6 , Djamila Issa  7 , Aart Beeker  8 , Yavuz M Bilgin  9 , Otto Visser  10 , Erik Van Werkhoven  11 , Margaretha G M Roemer  1 , Martine E D Chamuleau  1 , Tuna Mutis  12
Affiliations

Response to DA-EPOCH-R is associated with activation of 'fitter' cytotoxic T cells in patients with newly diagnosed double and triple hit high-grade B-cell lymphoma

A Vera De Jonge et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Natural killer cell and T-cell phenotype at baseline associated with response to DA-EPOCH-R. (A) Percentages of NKG2D+ natural killer (NK) cells as percentages of CD56bright and CD56dim NK cells and (B) percentages of CD16+ or CD56bright NK cells as percentages of total NK cells for patients who at the end of DA-EPOCH-R achieved complete metabolic remission (CMR) (blue) or did not achieve CMR (red). (C) Percentages of kill of K562 and degranulation as measured by CD107a/b surface expression on NK cells after 4-hour co-culture of peripheral blood mononuclear cells (PBMC) with K562 cell line at day 1 of the first DA-EPOCH-R cycle for patients who achieved CMR (blue) or did not achieve CMR (red). Cytotoxicity is calculated relative to the amount of K562 cells without PBMC. (D and E) Percentages of CD4+, CD8+ T cells (D) and regulatory T cells (Tregs), CD4-CD8-, innate-like gδ-T cells (E). Details as in (A and B). For all box plots, the lower upper hinges correspond to the 25th and 75th percentiles. The middle hinge corresponds to the median. The whiskers extend from the largest to smallest value +/- 1.58*interquartile range. Outliers are plotted individually. Non-parametric Mann-Whitney U test between two groups was used for statistical analysis in which P<0.05 was considered significant.
Figure 2.
Figure 2.
Natural killer cell phenotype during DA-EPOCH-R. (A-D) Percentages of CD16+ and CD56bright natural killer (NK) cells (A), HLA-DR+ NK cells (B), CD57+, KLRG1+, TIGIT+ NK cells (C), NKG2A+ NK cells (D) collected at day 1 of the first (Start) and third (Mid) DA-EPOCH-R cycles, and after the fifth DA-EPOCH-R cycle (End; end-of-treatment) for patients who at the end of DA-EPOCH-R achieved complete metabolic remission (CMR) (blue) or did not achieve CMR (red). (E) DNAM-1+ NK cells. Details as in (A). Linear mixed effect models were used for statistical analysis. For all box plots, the lower upper hinges correspond to the 25th and 75th percentiles. The middle hinge corresponds to the median. The whiskers extend from the largest to smallest value +/- 1.58*interquartile range. Outliers are plotted individually. P<0.05 was considered significant.
Figure 3.
Figure 3.
T-cell phenotype during DA-EPOCH-R. (A and B) Percentages of HLA-DR+ and CD38+ CD4+ and CD8+ T cells (A) and PD-1+ CD4+, CD8+, innate-like γδ-T cells and regulatory T cells (Tregs) (B) as percentages of total T cells collected at day 1 of the first (Start) and third (Mid) DA-EPOCH-R cycles, and after the fifth DA-EPOCH-R cycle (End; end-of-treatment) for patients who at the end of DA-EPOCH-R achieved complete metabolic remission (CMR) (blue) or did not achieve CMR (red). (C) Percentages of CD4+ T cells positive for interferon-γ and TNF-a after 4-hour stimulation with PMA/ionomysin at day 1 of the first (Start) and after the fifth (End) DA-EPOCH-R cycles for patients who at the end of DA-EPOCH-R achieved CMR (blue) or did not achieve CMR (red). (D) Percentages of PD-1+ CD8+ (E) as percentage of total T cells at the 3rd (Mid) and 5th (End) DA-EPOCH-R cycles for patients who at the end of DA-EPOCH-R achieved CMR (blue) or did not achieve CMR (red). P<0.05 was considered significant.
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