2. Academic Validation
  3. Chitosan oligosaccharide regulates AMPK and STAT1 pathways synergistically to mediate PD-L1 expression for cancer chemoimmunotherapy

Chitosan oligosaccharide regulates AMPK and STAT1 pathways synergistically to mediate PD-L1 expression for cancer chemoimmunotherapy

  • Carbohydr Polym. 2022 Feb 1:277:118869. doi: 10.1016/j.carbpol.2021.118869.
Jiashe Chen 1,  Zaigang Zhou 2,  Chunjuan Zheng 3,  Yu Liu 3,  Ruiqi Hao 1,  Xiaolin Ji 1,  Qiaoer Xi 1,  Jianliang Shen 4,  Zhiming Li 5
Affiliations

Affiliations

  • 1 Department of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China. Electronic address: [email protected].
  • 3 State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China.
  • 4 State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China. Electronic address: [email protected].
  • 5 Department of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: [email protected].
PMID: 34893274 DOI: 10.1016/j.carbpol.2021.118869
Abstract

After regular chemotherapy, the expression of programmed cell death ligand 1 (PD-L1) in almost all kinds of cancers is significantly increased, leading to reduced efficacy of T cell mediated immune killing in tumors. To solve this, a lot of PD-L1 antibodies were produced and used, but their high cost and serious toxic side effects still limit its usage. Recently, small molecule compounds that could effectively regulate PD-L1 expression possess the edges to solve the problems of PD-L1 antibodies. Chitosan oligosaccharide (COS), a biomaterial derived from the N-deacetylation product of chitin, has a broad spectrum of biological activities in treating tumors. However, the mechanism of its anti-cancer effect is still not well understood. Here, for the first time, we clearly identified that COS could inhibit the upregulated PD-L1 expression induced by interferon γ (IFN-γ) in various tumors via the AMPK activation and STAT1 inhibition. Besides, COS itself significantly restricted the growth of CT26 tumors by enhancing the T cell infiltration in tumors. Furthermore, we observed that combining COS with Gemcitabine (GEM), one of the typical chemotherapeutic drugs, leaded to a more remarkable tumor remission. Therefore, it was demonstrated that COS could be used as a useful way to improve the efficacy of existing chemotherapies by effective PD-L1 downregulation.

Keywords

AMP-activated protein kinase; Chemotherapy; Chitosan oligosaccharide; PD-L1; STAT1 signaling.

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