Sitagliptin and Cancer Immunotherapy

Sitagliptin is a drug that is commonly used to treat type 2 diabetes. It works by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4), which can lead to increased levels of the hormone glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion and can improve glucose control.

While sitagliptin is not typically used as a cancer treatment, there is some research suggesting that it may have potential as an immunotherapy agent for cancer. In preclinical studies, sitagliptin has been shown to enhance the anti-tumor immune response and increase the infiltration of immune cells into the tumor microenvironment.

PD-1 (programmed cell death protein 1) is another protein that is expressed on the surface of T cells and acts as a negative regulator of the immune response. Antibodies that block PD-1 or its ligand, PD-L1, have been shown to be effective in the treatment of several types of cancer.

There is some research suggesting that sitagliptin may enhance the activity of both CTLA-4 and PD-1 blockade in cancer immunotherapy. For example, a study published in the journal Cancer Immunology Research in 2018 showed that treatment with sitagliptin enhanced the anti-tumor immune response and improved the efficacy of PD-1 blockade in mouse models of lung cancer.

The researchers suggested that sitagliptin may enhance the activity of CTLA-4 and PD-1 blockade by modulating the immune system and increasing the infiltration of immune cells into the tumor microenvironment. In addition, sitagliptin has been shown to increase the expression of PD-L1 on cancer cells, which may sensitize them to PD-1 blockade.

While these findings are promising, more research is needed to fully understand the potential benefits of sitagliptin in combination with CTLA-4 and PD-1 blockade, and to determine the most effective doses and formulations for use in cancer patients. Clinical trials evaluating the use of sitagliptin in combination with immune checkpoint inhibitors are currently underway.

Reference: Wilson, A. L. (2021). DPP4 inhibitor sitagliptin enhances lymphocyte recruitment and prolongs survival in a syngeneic ovarian cancer mouse model. Cancers, 487.