2. Academic Validation
  3. Cordyceps militaris polysaccharide converts immunosuppressive macrophages into M1-like phenotype and activates T lymphocytes by inhibiting the PD-L1/PD-1 axis between TAMs and T lymphocytes

Cordyceps militaris polysaccharide converts immunosuppressive macrophages into M1-like phenotype and activates T lymphocytes by inhibiting the PD-L1/PD-1 axis between TAMs and T lymphocytes

  • Int J Biol Macromol. 2020 May 1;150:261-280. doi: 10.1016/j.ijbiomac.2020.02.050.
Sixue Bi 1,  Weijuan Huang 2,  Shan Chen 3,  Chunhua Huang 3,  Chunlei Li 1,  Zhongyi Guo 2,  Jianing Yang 1,  Jianhua Zhu 4,  Liyan Song 5,  Rongmin Yu 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.
  • 2 Biotechnological Institute of Chinese Materia Medica, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.
  • 3 Department of Natural Products Chemistry, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.
  • 4 Department of Natural Products Chemistry, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address: tzhujh@jnu.edu.cn.
  • 5 Department of Pharmacology, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address: tsly@jnu.edu.cn.
  • 6 Biotechnological Institute of Chinese Materia Medica, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China; Department of Natural Products Chemistry, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address: tyrm@jnu.edu.cn.
PMID: 32044366 DOI: 10.1016/j.ijbiomac.2020.02.050
Abstract

Tumour-associated macrophages (TAMs) inhibit the killing effect of T lymphocytes on tumour cells through the immunocheckpoint programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis. TAMs-targeted therapy is a promising approach that could be used to reverse the immunosuppressive tumour microenvironment. Here, we further report CMPB90-1, a novel natural polysaccharide from Cordyceps militaris, could function as an anti-tumour modulator that resets TAMs from a tumour-promoting M2 phenotype to a tumour-killing M1 phenotype. This process involves reversing the functional inhibition of T lymphocytes by inhibiting the PD-L1/PD-1 axis between TAMs and T lymphocytes. Mechanistically, the membrane receptor of CMPB90-1 binding to M2 macrophages was identified by tandem mass spectrometry. CMPB90-1 converts immunosuppressive TAMs via binding to Toll-like Receptor 2 (TLR2), which causes the release of CA2+ and the activation of p38, Akt and NF-κB, or ERK. This process then leads to the polarization of TAMs from M2 phenotype to the M1 phenotype. In vivo experiment shows that CMPB90-1 is able to polarize TAMs into the M1 phenotype and has anti-tumour effects with improved safety. Additionally, the anti-tumour effects of CMPB90-1 in vivo depend on the phenotypic conversion of TAMs. The results demonstrated that CMPB90-1 could be developed as a potential immune-oncology treatment reagent.

Keywords

Cordyceps militaris polysaccharide; PD-L1/PD-1; TLR2; Tumour-associated macrophages.

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