PAX5 haploinsufficiency induced CD8+ T cells dysfunction or exhaustion by high expression of immune inhibitory-related molecules
PAX5 haploinsufficiency induced CD8+ T cells dysfunction or exhaustion by high expression of immune inhibitory-related molecules
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DOI：
10.1016/j.ctarc.2021.100437
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发表时间：
2021
影响因子：
--
通讯作者：
周建峰
中科院分区：
文献类型：
--
作者：
梁密;龚端豪;王磊;梁雪;孟姣;黄伟;周建峰
Purpose: PAX5 haploinsufficiency promoting tumorigenesis is related to immune escape. But the mechanisms of .PAX5 mutations inducing tumor immune escape have not been clarified. Our aim was to study how PAX5 .haploinsufficiency influences effector CD8 + T cells in tumor microenvironment. .Methods: We estimated the proportions of 22 immune cell types and the expressions of immune inhibitory-related .molecules based on gene expression profiles (GEPs) from children’s B- acute lymphoblastic leukemia(B-ALL) with .PAX5 mutations by CIBERSORT, an established algorithm. We constructed the PAX5 haplodeletion A20 cell lines, .built allografted A20 tumor models and evaluated the effect of PAX5 haplodeletion on immune inhibitory-related .molecules in the tumor microenvironment (TME). .Results: Our results indicated the percentages of T cells in bone marrow of children’s B-ALL with PAX5 mutations .were not statistically different from that in bone marrow of B-ALL without PAX5 mutations, except for T .follicular helper (Tfh) cells. But a variety of up-regulated immune inhibitory-related molecules in bone marrow .of children’s B- ALL with PAX5 mutations were identified. By different approaches, we found that several immune inhibitory-related molecules of CD8+ T cells in TME of PAX5 haplodeletion clones such as TIM3, NR4A1 .and BATF, were increased significantly compared with that of PAX5 wild type control. The IFN-ɤ of CD8+ T cells .in TME of PAX5 haplodeletion tumors was decreased significantly compared with that of PAX5 wild type control. .Conclusion: Our study showed that PAX5 haploinsufficiency induced CD8+ T cells dysfunction or exhaustion by .high expression of TIM3, NR4A1 and BATF in the CD8+ T cells of TME.
