Fig 1: IDO and TDO – Tryptophan Catabolic Pathways

Trpytophan (trp) is an important and essential amino acid that has a variety of functions within the cell. In addition to being incorporated into the polypeptide chain of proteins, various catabolic pathways can produce a number of functional Trp derivatives. Trp is the biosynthetic precursor of the co-factor NAD, a number of antibiotics, and the neurotransmitters serotonin and melatonin.

The factors regulating the fate of Trp in the cell have yet to be fully elucidated, but likely involve specific enzymes that may vary in expression levels or with the cell type (Fig 1 – Shown is a depiction of two important tryptophan catabolic pathways and the enzymes that participate in the process).

Which roles do IDO and TDO play in Immunotherapy? Immune evasion is one of the identifying hallmarks of cancer and researchers are investigating the complex mechanisms that enable cancer cells to evade the host’s immune system. In the context of a tumor, Tryptophan (Trp or L-Trp) catabolizing enzymes have been shown to assist cancer cells in immune evasion.

In previous blogs, I invited you to join me in exploring the relevance of the following pathways:

• B7-1 : CD28, B7-1 : CTLA4
• BLTA:HVEM, CD47:SIRPα
• GITR:GITRL
• CD40:CD40L
• PD-1/PD-L1/PD-L2
• CD137:CD137L

Today I’d like to focus on the IDO pathway.