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.
Highlights
Colon cancer is one of the most common malignant tumors in the digestive system
We found that the combination of oxaliplatin and D-MT significantly inhibited tumor growth, prolonged the survival of tumor-bearing mice, increased the cell apoptosis
This study provided a new therapeutic strategy for colon cancer treatment in the clinic, especially for patients with oxaliplatin resistance
Summary
It has been proved that indoleamine dioxygenase 2,3 (IDO), an immune checkpoint, is a result of tolerance to chemotherapy. The anti-tumor effect of treatment with oxaliplatin and DMT, an IDO inhibitor, on the mice was observed by recording the tumor growth and survival of the mice, and detecting T cell infiltration in tumor tissues and the ratios of immune cells in the spleen by corresponding methods
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