2. Academic Validation
  3. A β-1,3/1,6-glucan enhances anti-tumor effects of PD1 antibody by reprogramming tumor microenvironment

A β-1,3/1,6-glucan enhances anti-tumor effects of PD1 antibody by reprogramming tumor microenvironment

  • Int J Biol Macromol. 2024 Nov;279(Pt 1):134660. doi: 10.1016/j.ijbiomac.2024.134660.
Qiaoling Song 1,  Yuting Xu 2,  Minghui Zhang 2,  Lijuan Wu 1,  Shan Liu 3,  Youjing Lv 4,  Ting Hu 4,  Jun Zhao 3,  Xiaonan Zhang 3,  Xiaohan Xu 2,  Quancai Li 4,  Mingming Zhou 3,  Xinxin Zhang 3,  Peizhe Lu 5,  Guangli Yu 6,  Chenyang Zhao 7,  Jinbo Yang 8
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Innovation Platform of Marine Drug Screening & Evaluation, Qingdao Marine Science and Technology Center, Qingdao 266100, China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China.
  • 2 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
  • 3 Innovation Platform of Marine Drug Screening & Evaluation, Qingdao Marine Science and Technology Center, Qingdao 266100, China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China.
  • 4 Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China.
  • 5 Department of Neuroscience, University of Michigan, Ann Arbor, MI 48103, USA.
  • 6 Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Laoshan Laboratory, Qingdao 266237, China.
  • 7 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Innovation Platform of Marine Drug Screening & Evaluation, Qingdao Marine Science and Technology Center, Qingdao 266100, China. Electronic address: zhaoc2@ccf.org.
  • 8 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Innovation Platform of Marine Drug Screening & Evaluation, Qingdao Marine Science and Technology Center, Qingdao 266100, China. Electronic address: yangjb@ouc.edu.cn.
PMID: 39134196 DOI: 10.1016/j.ijbiomac.2024.134660
Abstract

Checkpoint blockades have emerged as a frontline approach in Cancer management, designed to enhance the adaptive immune response against tumors. However, its clinical efficacy is limited to a narrow range of tumor types, which necessitates the exploration of novel strategies that target another main branch of the immune system. One such potential strategy is the therapeutic modulation of Pattern Recognition Receptors (PRRs) pathways in innate immune cells, which have shown promise in tumor eradication. Previously, a β-1,3/1,6-glucan with high purity from Durvillaea antarctica (BG136) was reported by our group to exhibit pan-antitumor effects. In the current study, we systemically studied the antitumor activity of BG136 in combination with anti-PD1 antibody in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggested that BG136 enhanced the antitumor immunity of anti-PD1 antibody by reprogramming the tumor microenvironment to become more proinflammatory. In addition, an increase in innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, and a decrease in ascorbate and aldarate metabolism were also found. These findings provide mechanistic insights that support the potent antitumor efficacy of BG136 when combined with Immune Checkpoint Inhibitor antibodies.

Keywords

Anti-tumor; Immunotherapy; Metabolomics; Transcriptomics; Tumor microenvironment; β-Glucan.

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