Cordycepin enhances the Anticancer efficacy of PD-L1 blockade by modulating the tumor microenvironment of colon cancer

Eur J Pharmacol. 2024 Dec 15:985:177089. doi: 10.1016/j.ejphar.2024.177089. Epub 2024 Nov 1.

Abstract

Background: PD-L1 blockade has been found to be effective in treating multiple malignancies. Combined therapy is proposed to provide better therapeutic effects. Cordycepin, a prominent bioactive compound found in cordyceps, can inhibit the development of various cancers.

Purpose: This study aimed to determine the efficacy of combined anti-PD-L1 antibody and cordycepin in tumor treatment.

Methods: A single-cell RNA sequencing was used to analyze the mechanism of combined treatment.

Results: Combination therapy of anti-PD-L1 and cordycepin significantly inhibited tumor growth by regulating the T cell ratio and improving the function of CD8+T cells. Furthermore, cordycepin promoted the reprogramming of type-II macrophages into type-I macrophages, a process confirmed through flow cytometry analysis of the underlying mechanism.

Conclusion: Our findings demonstrate that the combination of anti-PD-L1 and cordycepin effectively suppressed tumor growth by regulating the proportion of T cells and reprograming type-II macrophages.

Keywords: Anti-PD-L1; Cordycepin; Macrophage; Tissue-resident memory T cells; Tumor microenvironment.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen* / antagonists & inhibitors
  • B7-H1 Antigen* / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / pathology
  • Deoxyadenosines* / pharmacology
  • Deoxyadenosines* / therapeutic use
  • Drug Synergism
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • Tumor Microenvironment* / drug effects

Substances

  • cordycepin
  • Deoxyadenosines
  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors