D-MT prompts the anti-tumor effect of oxaliplatin by inhibiting IDO expression in a mouse model of colon cancer

Int Immunopharmacol. 2021 Dec;101(Pt A):108203. doi: 10.1016/j.intimp.2021.108203. Epub 2021 Oct 11.

Abstract

Colon cancer is one of the most common malignant tumors in the digestive system. Although oxaliplatin, a chemotherapy drug, has been clinically used to treat colon cancer, its therapeutic effect is unsatisfactory. It has been proved that indoleamine dioxygenase 2,3 (IDO) is a tumor immunosuppressive factor for the immune response. Herein, an IDO inhibitor, D-MT (indoximod, 1-Methyl-D-tryptophan), was combined with oxaliplatin to treat colon cancer in mice. T cell infiltration in tumor tissues, the ratios of immune cells in the spleens, and the tumor growth and survival of the mice were detected and recorded. The results showed that the combination of oxaliplatin and D-MT significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. More importantly, the combination treatment increased the ratios of CD4+ T, CD8+ T and NK cells from the spleen in tumor-bearing mice, and prompted T cell infiltration in tumor tissues. This study provided a new therapeutic strategy for colon cancer treatment in the clinic, especially for patients with oxaliplatin resistance.

Keywords: Anti-tumor immune response; Colon cancer; IDO; Oxaliplatin.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Blotting, Western
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Oxaliplatin / therapeutic use*
  • Tryptophan / analogs & derivatives*
  • Tryptophan / therapeutic use

Substances

  • Antineoplastic Agents
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Oxaliplatin
  • Tryptophan
  • 1-methyltryptophan