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[Research progress on TCM intervention in cancer based on PD-1/PD-L1 signaling pathway]

Ya-Jie Lin1, Shuai Ma1, Lei Chen1

  • 1the Second Clinical Medical College,Henan University of Chinese Medicine Zhengzhou 450053,China First Oncology Ward,the Second Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450002,China.

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica
|August 2, 2026
PubMed

Insights

Traditional Chinese Medicine (TCM) compounds can regulate the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway to enhance cancer immunotherapy. These multi-target interventions offer new strategies to overcome resistance and improve patient outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • The PD-1/PD-L1 pathway is crucial for tumor immune evasion, suppressing anti-tumor immunity via T-cell exhaustion, Treg expansion, M2 macrophage polarization, NK cell dysfunction, and metabolic disruption.
  • Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 show efficacy in solid tumors but face limitations due to resistance, irAEs, and TME heterogeneity, affecting 60-70% of patients.
  • Single-target blockade is insufficient, necessitating multidimensional interventions to overcome immune escape.

Purpose of the Study:

  • To systematically review the research progress on TCM active ingredients, compounds, and patent medicines in cancer immunotherapy, focusing on the PD-1/PD-L1 pathway.
  • To analyze the immunoregulatory networks of TCM in modulating the PD-1/PD-L1 pathway.
  • To provide theoretical insights and translational directions for optimizing cancer immunotherapy strategies using TCM.

Main Methods:

  • Literature review focusing on studies investigating TCM active ingredients, compounds, and patent medicines.
  • Analysis of mechanisms by which TCM regulates the PD-1/PD-L1 pathway and enhances anti-tumor immunity.
  • Examination of TCM's role in modulating signaling pathways, epigenetic changes, cellular metabolism, and the tumor microenvironment.

Main Results:

  • TCM active ingredients and compounds demonstrate the ability to regulate the PD-1/PD-L1 pathway through multiple targets.
  • TCM interventions modulate key signaling pathways, mediate epigenetic changes, reprogram cellular metabolism, and reshape the immunosuppressive tumor microenvironment.
  • These multi-target actions of TCM enhance anti-tumor immune responses.

Conclusions:

  • TCM offers a promising avenue for cancer immunotherapy by targeting the PD-1/PD-L1 pathway via multi-dimensional mechanisms.
  • TCM-based strategies have the potential to overcome ICI resistance and improve therapeutic efficacy.
  • Further research into TCM's immunoregulatory networks can provide valuable insights for developing novel cancer treatment strategies.
Keywords:
PD-1/PD-L1TCMcancer immunotherapyimmune checkpoint inhibitorsresearch progress

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