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- Title
PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells.
- Authors
Li, Qing; Zhang, Liren; You, Wenhua; Xu, Jiali; Dai, Jingjing; Hua, Dongxu; Zhang, Ruizhi; Yao, Feifan; Zhou, Suiqing; Huang, Wei; Dai, Yongjiu; Zhang, Yu; Baheti, Tasiken; Qian, Xiaofeng; Pu, Liyong; Xu, Jing; Xia, Yongxiang; Zhang, Chuanyong; Tang, Jinhai; Wang, Xuehao
- Abstract
Programmed death receptor-1 (PD-1) blockade have achieved some efficacy but only in a fraction of patients with hepatocellular carcinoma (HCC). Programmed cell death 1 ligand 1 (PD-L1) binds to its receptor PD1 on T cells to dampen antigen-tumor immune responses. However, the mechanisms underlying PD-L1 regulation are not fully elucidated. Herein, we identify that tumoral Prdm1 overexpression inhibits cell growth in immune-deficient mouse models. Further, tumoral Prdm1 overexpression upregulates PD-L1 levels, dampening anti-tumor immunity in vivo, and neutralizes the anti-tumor efficacy of Prdm1 overexpression in immune-competent mouse models. Mechanistically, PRDM1 enhances USP22 transcription, thus reducing SPI1 protein degradation through deubiquitination, which enhances PD-L1 transcription. Functionally, PD-1 mAb treatment reinforces the efficacy of Prdm1-overexpressing HCC immune-competent mouse models. Collectively, we demonstrate that the PRDM1-USP22-SPI1 axis regulates PD-L1 levels, resulting in infiltrated CD8+ T cell exhaustion. Furthermore, PRDM1 overexpression combined with PD-(L)1 mAb treatment provides a therapeutic strategy for HCC treatment. Members of the PRDI-BF1 and RIZ homology domain (PRDM) family have been involved in the regulation of several pathological conditions, including cancer. Here the authors show that PRDM1/BLIMP1 promotes immune evasion by regulating PD-L1 expression in hepatocellular carcinoma cells.
- Subjects
PROGRAMMED cell death 1 receptors; PROGRAMMED death-ligand 1; HEPATOCELLULAR carcinoma; T cell receptors
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35469-x