Fig. 4: Exhausted CD8+ T cells during disease progression in patients with PD. | Nature Communications

Fig. 4: Exhausted CD8+ T cells during disease progression in patients with PD.

From: Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma

Fig. 4

a T cells in 16 subclusters were scored according to the dysfunctional signature and immunosuppressive signature. b The dysfunctional signature and immunosuppressive signature scores of CD8 Teff and CD8 Tex 1-6 subclusters were assessed in patients with PD before CAR-T cell therapy, during CAR-T cell expansion, and during disease progression. n = 8374 CD8 T cells were used for visualization, excluding those with a score of 0 due to the absence of detected gene expression. In the boxplot, a white dot within the box marks the median. The bottom and top of the box are located at the 25th and 75th percentiles, respectively. The bars represent values more than 1.5 times the interquartile range from the border of each box. The p values were calculated using the Wilcoxon rank-sum test. Two-sided p values were calculated. c GSEA was used to assess the upregulated and downregulated pathways of differentially expressed genes among before CAR-T cell therapy, during CAR-T cell expansion, and during disease progression targeting CD8 Teff and CD8 Tex cells. d Trajectory analysis of CD8+ T cells. e CD8+ T cells were divided into three main states: in state 1, immunoactivated Teff was in equilibrium with exhausted Tex and Prolif; in state 2, Tex cells were the dominant cells; and in state 3, the proportion of Tex cells was significantly lower than that in state 2, but the proportion of Prolif cells with exhaustion characteristics was significantly increased. According to the distribution characteristics of each state at different time points, CD8+ T cells were mainly distributed in state 1 before CAR-T cell therapy, in state 2 during CAR-T cell expansion, and in state 3 during disease progression. f The expression of genes related to the effector molecular and transcription factors of CD8 Teff cells as well as the inhibitory molecules and transcription factors of CD8 Tex cells was assessed. Data are shown as mean ± s.e.m. Statistical analysis was performed using two-way ANOVA with Tukey’s multiple comparison tests.

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