Nano‐Regulator Inhibits Tumor Immune Escape via the “Two‐Way Regulation” Epigenetic Therapy Strategy

Abstract: Tumor immune escape caused by low levels of tumor immunogenicity and immune checkpoint‐dependent suppression limits the immunotherapeutic effect. Herein, a “two‐way regulation” epigenetic therapeutic strategy is proposed using a novel nano‐regulator that inhibits tumor immune escape by upregulating expression of tumor‐associated antigens (TAAs) to improve immunogenicity and downregulating programmed cell death 1 ligand 1 (PD‐L1) expression to block programmed death‐1 (PD‐1)/PD‐L1. To engineer the nano‐regulator, the DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) and the bromodomain‐containing protein 4 (BRD4) inhibitor JQ1 are co‐loaded into the cationic liposomes with condensing the toll‐like receptor 9 (TLR9) agonist cytosine‐phosphate‐guanine (CpG) via electrostatic interactions to obtain G‐J/ZL. Then, asparagine–glycine–arginine (NGR) modified material carboxymethyl‐chitosan (CMCS) is coated on the surface of G‐J/ZL to construct CG‐J/ZL. CG‐J/ZL is shown to target tumor tissue and disassemble under the acidic tumor microenvironment (TME). Zeb upregulated TAAs expression to improve the immunogenicity; JQ1 inhibited PD‐L1 expression to block immune checkpoint; CpG promote dendritic cell (DC) maturation and reactivated the ability of tumour‐associated macrophages (TAM) to kill tumor cells. Taken together, these results demonstrate that the nano‐regulator CG‐J/ZL can upregulate TAAs expression to enhance T‐cell infiltration and downregulate PD‐L1 expression to improve the recognition of tumor cells by T‐cells, representing a promising strategy to improve antitumor immune response.

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• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Nano‐Regulator Inhibits Tumor Immune Escape via the “Two‐Way Regulation” Epigenetic Therapy Strategy ; day:18 ; month:12 ; year:2023 ; extent:11 ; Advanced science ; (18.12.2023) (gesamt 11)

Contributors, Places and Time

• Creator: Liang, Shuang ; Liu, Meichen ; Mu, Weiwei ; Gao, Tong ; Gao, Shuying ; Fu, Shunli ; Yuan, Shijun ; Liu, Jinhu ; Liu, Yongjun ; Jiang, Dandan ; Zhang, Na

Further information

• DOI: 10.1002/advs.202305275
• URN: urn:nbn:de:101:1-2023121914195117879922
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.