表观遗传修饰对肿瘤PD-L1表达调控的研究进展

doi:10.3760/cma.j.cn371439-20220323-00065

摘要/Abstract

摘要：

肿瘤细胞表达程序性死亡蛋白配体-1（PD-L1）是引起免疫逃逸的主要机制,也是免疫检查点抑制剂治疗疗效的预测因素。PD-L1表达受多种机制调控,其中DNA甲基化、组蛋白修饰、非编码RNA等表观遗传修饰可通过调控PD-L1的表达促进肿瘤发生发展和产生耐药。明确其调控机制可为肿瘤临床免疫治疗带来新的思路。

关键词: 肿瘤, 表观遗传调控, PD-L1

Abstract:

Tumor cells expression of programmed death ligand-1 （PD-L1） is a major mechanism of immune escape and a predictor of therapeutic efficacy of immune checkpoint inhibitors. The expression of PD-L1 is regulated by a variety of mechanisms, among which epigenetic modifications such as DNA methylation, histone modification and non-coding RNA can promote the occurrence, development and drug resistance of tumors by regulating the expression of PD-L1. To clarify its regulation mechanism can bring new ideas for clinical immunotherapy of tumors.

Key words: Neoplams, Epigenetic regulation, PD-L1

王悦, 呼群, 侯英伟. 表观遗传修饰对肿瘤PD-L1表达调控的研究进展[J]. 国际肿瘤学杂志, 2022, 49(6): 345-348.

Wang Yue, Hu Qun, Hou Yingwei. Research progress in influences of epigenetic modifications on PD-L1 expression in tumors[J]. Journal of International Oncology, 2022, 49(6): 345-348.

参考文献 33

[1]	Zhang H, Dai Z, Wu W, et al. Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer[J]. J Exp Clin Cancer Res, 2021, 40(1): 184. DOI: 10.1186/s13046-021-01987-7. doi: 10.1186/s13046-021-01987-7
[2]	Skourti E, Dhillon P. Cancer epigenetics: promises and pitfalls for cancer therapy[J]. FEBS J, 2022, 289(5): 1156-1159. DOI: 10.1111/febs.16395. doi: 10.1111/febs.16395 pmid: 35233949
[3]	Ao C, Gao L, Yu L. Research progress in predicting DNA methylation modifications and the relation with human diseases[J]. Curr Med Chem, 2022, 29(5): 822-836. DOI: 10.2174/0929867328666210917115733. doi: 10.2174/0929867328666210917115733
[4]	Micevic G, Thakral D, McGeary M, et al. PD-L1 methylation regulates PD-L1 expression and is associated with melanoma survival[J]. Pigment Cell Melanoma Res, 2019, 32(3): 435-440. DOI: 10.1111/pcmr.12745. doi: 10.1111/pcmr.12745
[5]	Xu J, Wei L, Liu H, et al. CD274 (PD-L1) methylation is an independent predictor for bladder cancer patients' survival[J]. Cancer Invest, 2022, 40(3): 228-233. DOI: 10.1080/07357907.2022.2028805. doi: 10.1080/07357907.2022.2028805
[6]	Palicelli A, Croci S, Bisagni A, et al. What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. part 5: epigenetic regulation of PD-L1[J]. Int J Mol Sci, 2021, 22(22): 12314. DOI: 10.3390/ijms222212314. doi: 10.3390/ijms222212314
[7]	Asgarova A, Asgarov K, Godet Y, et al. PD-L1 expression is regulated by both DNA methylation and NF-kB during EMT signaling in non-small cell lung carcinoma[J]. Oncoimmunology, 2018, 7(5): e1423170. DOI: 10.1080/2162402X.2017.1423170. doi: 10.1080/2162402X.2017.1423170
[8]	Huang KC, Chiang SF, Chen WT, et al. Decitabine augments chemotherapy-induced PD-L1 upregulation for PD-L1 blockade in colorectal cancer[J]. Cancers (Basel), 2020, 12(2): 462. DOI: 10.3390/cancers12020462. doi: 10.3390/cancers12020462
[9]	Li X, Wang Z, Huang J, et al. Specific Zinc finger-induced methylation of PD-L1 promoter inhibits its expression[J]. FEBS Open Bio, 2019, 9(6): 1063-1070. DOI: 10.1002/2211-5463.12568. doi: 10.1002/2211-5463.12568
[10]	Xu YP, Lv L, Liu Y, et al. Tumor suppressor TET2 promotes cancer immunity and immunotherapy efficacy[J]. J Clin Invest, 2019, 129(10): 4316-4331. DOI: 10.1172/JCI129317. doi: 10.1172/JCI129317
[11]	Shen Y, Liu L, Wang M, et al. TET2 inhibits PD-L1 gene expression in breast cancer cells through histone deacetylation[J]. Cancers (Basel), 2021, 13(9): 2207. DOI: 10.3390/cancers13092207. doi: 10.3390/cancers13092207
[12]	Lin Y, Qiu T, Wei G, et al. Role of histone post-translational modifications in inflammatory diseases[J]. Front Immunol, 2022, 13: 852272. DOI: 10.3389/fimmu.2022.852272. doi: 10.3389/fimmu.2022.852272
[13]	Ruzic D, Djoković N, Srdić-Rajić T, et al. Targeting histone deacetylases: opportunities for cancer treatment and chemoprevention[J]. Pharmaceutics, 2022, 14(1): 209. DOI: 10.3390/pharmaceutics14010209. doi: 10.3390/pharmaceutics14010209
[14]	Duan R, Du W, Guo W. EZH2: a novel target for cancer treatment[J]. J Hematol Oncol, 2020, 13(1): 104. DOI: 10.1186/s13045-020-00937-8. doi: 10.1186/s13045-020-00937-8
[15]	Zhao Y, Wang XX, Wu W, et al. EZH2 regulates PD-L1 expre-ssion via HIF-1α in non-small cell lung cancer cells[J]. Biochem Biophys Res Commun, 2019, 517(2): 201-209. DOI: 10.1016/j.bbrc.2019.07.039. doi: 10.1016/j.bbrc.2019.07.039
[16]	Xiao G, Jin LL, Liu CQ, et al. EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma[J]. J Immunother Cancer, 2019, 7(1): 300. DOI: 10.1186/s40425-019-0784-9. doi: 10.1186/s40425-019-0784-9
[17]	Xiong W, Deng H, Huang C, et al. MLL3 enhances the trans-cription of PD-L1 and regulates anti-tumor immunity[J]. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(2): 454-463. DOI: 10.1016/j.bbadis.2018.10.027. doi: 10.1016/j.bbadis.2018.10.027
[18]	Xu S, Wang X, Yang Y, et al. LSD1 silencing contributes to enhanced efficacy of anti-CD47/PD-L1 immunotherapy in cervical cancer[J]. Cell Death Dis, 2021, 12(4): 282. DOI: 10.1038/s41419-021-03556-4. doi: 10.1038/s41419-021-03556-4
[19]	Shen DD, Pang JR, Bi YP, et al. LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in gastric cancer[J]. Mol Cancer, 2022, 21(1): 75. DOI: 10.1186/s12943-022-01557-1. doi: 10.1186/s12943-022-01557-1
[20]	Rajan PK, Udoh UA, Sanabria JD, et al. The role of histone acetylation-/methylation-mediated apoptotic gene regulation in hepatocellular carcinoma[J]. Int J Mol Sci, 2020, 21(23): 8894. DOI: 10.3390/ijms21238894. doi: 10.3390/ijms21238894
[21]	King J, Patel M, Chandrasekaran S. Metabolism, HDACs, and HDAC inhibitors: a systems biology perspective[J]. Metabolites, 2021, 11(11): 792. DOI: 10.3390/metabo11110792. doi: 10.3390/metabo11110792
[22]	Bondarev AD, Attwood MM, Jonsson J, et al. Recent developments of HDAC inhibitors: emerging indications and novel mole-cules[J]. Br J Clin Pharmacol, 2021, 87(12): 4577-4597. DOI: 10.1111/bcp.14889. doi: 10.1111/bcp.14889 pmid: 33971031
[23]	Yang Z, Zhang L, Liu J, et al. PD-L1 combined with HDAC9 is a useful prognostic predictor in hepatocellular carcinoma[J]. Transl Cancer Res, 2021, 10(5): 2305-2317. DOI: 10.21037/tcr-20-3415. doi: 10.21037/tcr-20-3415
[24]	Li X, Su X, Liu R, et al. HDAC inhibition potentiates anti-tumor activity of macrophages and enhances anti-PD-L1-mediated tumor suppression[J]. Oncogene, 2021, 40(10): 1836-1850. DOI: 10.1038/s41388-020-01636-x. doi: 10.1038/s41388-020-01636-x
[25]	Wang N, Wu R, Tang D, et al. The BET family in immunity and disease[J]. Signal Transduct Target Ther, 2021, 6(1): 23. DOI: 10.1038/s41392-020-00384-4. doi: 10.1038/s41392-020-00384-4
[26]	Andrieu GP, Shafran JS, Smith CL, et al. BET protein targeting suppresses the PD-1/PD-L1 pathway in triple-negative breast cancer and elicits anti-tumor immune response[J]. Cancer Lett, 2019, 465: 45-58. DOI: 10.1016/j.canlet.2019.08.013. doi: 10.1016/j.canlet.2019.08.013
[27]	Liu K, Zhou Z, Gao H, et al. JQ1, a BET-bromodomain inhibitor, inhibits human cancer growth and suppresses PD-L1 expression[J]. Cell Biol Int, 2019, 43(6): 642-650. DOI: 10.1002/cbin.11139. doi: 10.1002/cbin.11139
[28]	Jing X, Shao S, Zhang Y, et al. BRD4 inhibition suppresses PD-L1 expression in triple-negative breast cancer[J]. Exp Cell Res, 2020, 392(2): 112034. DOI: 10.1016/j.yexcr.2020.112034. doi: 10.1016/j.yexcr.2020.112034
[29]	Ali Syeda Z, Langden SSS, Munkhzul C, et al. Regulatory me-chanism of microRNA expression in cancer[J]. Int J Mol Sci, 2020, 21(5): 1723. DOI: 10.3390/ijms21051723. doi: 10.3390/ijms21051723
[30]	Feng S, Sun H, Zhu W. MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway[J]. Clin Transl Oncol, 2021, 23(3): 450-458. DOI: 10.1007/s12094-020-02439-y. doi: 10.1007/s12094-020-02439-y
[31]	Roshani Asl E, Rasmi Y, Baradaran B. MicroRNA-124-3p suppresses PD-L1 expression and inhibits tumorigenesis of colorectal cancer cells via modulating STAT3 signaling[J]. J Cell Physiol, 2021, 236(10): 7071-7087. DOI: 10.1002/jcp.30378. doi: 10.1002/jcp.30378 pmid: 33821473
[32]	Rasoolnezhad M, Safaralizadeh R, Hosseinpourfeizi MA, et al. miRNA-138-5p: a strong tumor suppressor targeting PD-L1 inhibits proliferation and motility of breast cancer cells and induces apoptosis[J]. Eur J Pharmacol, 2021, 896: 173933. DOI: 10.1016/j.ejphar.2021.173933. doi: 10.1016/j.ejphar.2021.173933
[33]	Miliotis C, Slack FJ. miR-105-5p regulates PD-L1 expression and tumor immunogenicity in gastric cancer[J]. Cancer Lett, 2021, 518: 115-126. DOI: 10.1016/j.canlet.2021.05.037. doi: 10.1016/j.canlet.2021.05.037