Fig. 1: Combined CREBBP and KMT2D haploinsufficiency accelerates murine lymphomagenesis, featuring a CD8+ T cell-depleted microenvironment. | Nature Communications

Fig. 1: Combined CREBBP and KMT2D haploinsufficiency accelerates murine lymphomagenesis, featuring a CD8+ T cell-depleted microenvironment.

From: Loss of CREBBP and KMT2D cooperate to accelerate lymphomagenesis and shape the lymphoma immune microenvironment

Fig. 1

a Experimental scheme for murine lymphomagenesis. BMT recipients: 8-weeks, female C57BL/6J mice. b Mouse spleen/body weight ratio. Mean ± SD, left to right: n = 6/8/8/8/8 and 6/7/7/7/7 mice. c Representative H&E and B220 IHC images of mouse spleen and lung sections. Scale bars: 200 pixels in spleen and 380 pixels in lung. d FACS analysis showing the frequency of splenic GC B cells (CD38-FAS+). Mean ± SD, n = 4 mice per genotype. e Mutation burden at IgH-VJ558-JH4 region in mouse lymphoma cells. n = 36 clones per genotype. f Kaplan–Meier survival curve of the lymphomagenic mice. n  =  20 mice per group. g, h FACS analysis showing the frequency of splenic (g) CD4+ and (h) CD8+ T cells. Mean ± SD, n = 4 mice per genotype. i, j FACS analysis showing the frequency of splenic naïve/CM/effector CD8 at day 116 (i) or exhausted CD8 (TCF1-TOX+) at day 116 and 235 (j). Mean ± SD, n = 4 mice per genotype. k Representative CD4 and CD8 IHC images of spleen sections. Scale bar = 200 pixels. l IHC based quantification of CD8+ cell frequency within B220+ B cell follicles. Mean ± SD, n = 7 mice per genotype. m Representative CD8 IHC images of human FL tissue microarrays (TMAs)35. Scale bar = 100 pixels. n CD8+ cell percentage among overall cellularity in human FL TMAs (left to right: n = 23, 43, 53, 109). Kruskal–Wallis test followed by Dunn’s multiple comparisons test. The box middle line marks the median. The vertical size of box denotes the interquartile range (IQR). The upper and lower hinges correspond to the 25th and 75th percentiles. The upper and lower whiskers extend to the maximum and minimum values that are within 1.5 × IQR from the hinges. o A summary of lymphoma microenvironment change in BCL2 + CK vs BCL2. Up and down arrows indicate population increase or decrease respectively in BCL2 + CK vs BCL2. CD8cm/eff/act/ex: central memory/effector/activated/exhausted CD8. P values were determined using ordinary one-way ANOVA followed by Tukey–Kramer’s multiple comparisons test (b, d, g–j, l), two-tailed Wilcoxon rank sum test (e), two-tailed log-rank test (f). Source data are provided as a Source Data file.

Back to article page