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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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Ganoderic acid T, a Ganoderma triterpenoid, modulates the tumor microenvironment and enhances the chemotherapy and

Suyu Chen1, Kuangdee Chen1, Yihsiu Lin1

  • 1Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan.

Toxicology and Applied Pharmacology
|August 14, 2024
PubMed

Insights

Ganoderic acid T (GAT) shows potent anti-cancer effects by downregulating galectin-1 (Gal-1) and improving the tumor microenvironment (TME). This natural compound enhances chemotherapy and immunotherapy efficacy for cancer treatment.

Area of Science:

  • Natural Products Chemistry
  • Cancer Biology
  • Immunology

Background:

  • Ganoderic acid T (GAT), a triterpenoid from Ganoderma lucidum, possesses anti-cancer properties.
  • The precise molecular mechanisms underlying GAT's anti-cancer activity are not fully understood.
  • Investigating GAT's role in the tumor microenvironment (TME) is crucial for understanding its therapeutic potential.

Purpose of the Study:

  • To elucidate the anti-cancer molecular mechanisms of Ganoderic acid T (GAT).
  • To explore the therapeutic applications of GAT in cancer treatment.
  • To evaluate GAT's impact on the tumor microenvironment (TME) and its synergistic effects with conventional therapies.

Main Methods:

  • Utilized an ES-2 orthotopic ovarian cancer mouse model and EMT6 syngeneic mammary cancer model.
  • Performed proteomic analysis to identify GAT's molecular targets.
  • Conducted molecular docking studies to assess GAT-galectin-1 (Gal-1) interaction.
  • Evaluated GAT's efficacy in combination with paclitaxel chemotherapy and anti-PD-L1 immunotherapy.

Main Results:

  • GAT demonstrated significant anti-cancer activity, reducing tumor burden and altering the TME by decreasing α-SMA+ cells and increasing tumor-infiltrating lymphocytes (TILs).
  • Proteomic analysis revealed GAT downregulates galectin-1 (Gal-1), a key TME modulator, through ubiquitination.
  • GAT synergized with paclitaxel, increasing intratumoral drug concentration and reducing tumor size.
  • GAT enhanced anti-PD-L1 immunotherapy efficacy, increasing CD8+ cell infiltration in the EMT6 model.

Conclusions:

  • Ganoderic acid T (GAT) exhibits potent anti-cancer effects by modulating the tumor microenvironment (TME) and downregulating galectin-1 (Gal-1).
  • GAT significantly enhances the efficacy of both chemotherapy (paclitaxel) and immunotherapy (anti-PD-L1).
  • GAT represents a promising therapeutic agent for cancer treatment, potentially improving outcomes when combined with existing therapies.
Keywords:
Anti-cancerGalectin-1Ganoderic acid TImmunotherapyTumor microenvironment

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