Certain enzymes expressed by tumors disable T cells by depriving them of a key amino acid known as tryptophan. The expression of one of them, IDO, has been exhaustively studied. But little is known about the expression of the other, TDO, or about its effects on the immune system. In a December paper in Cancer Immunology Research, a team led by Ludwig’s Benoît Van den Eynde reported their use of a novel TDO-specific monoclonal antibody to explore TDO’s role in cancer biology. Benoît and colleagues showed that TDO is expressed by the majority of human cancers and plays an immunosuppressive role in hepatocellular carcinoma—the most common type of primary liver cancer—where it could be a prime immunotherapeutic target. They found that approximately 25% of glioblastomas and 10% of kidney cancers also expressed TDO in tumor cells. In many other cancers, TDO seems to be involved not so much in immune suppression as in angiogenesis, or the generation of tumor-feeding blood vessels. In either case, the enzyme does appear to hold some promise as a target for cancer therapy.
This article appeared in the April 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).