|Histological section of two mouse melanomas - (a) untreated |
and (b) treated with sitagliptin, a specific DPP4 inhibitor.
Stain: hematoxylin and eosin; scale bar: 500 mm.
(Credit: Institut Pasteur)
Scientists have successfully increased the infiltration of immune cells into tumors, thus inducing the immune system to block tumor growth. In an article published in Nature Immunology, the scientists show that, in combination with existing immunotherapies, this process efficiently destroys cancer cells.
Chemokines are small molecules that can attract immune cells towards inflammatory tissues, acting for example during tumor development or upon infection, in order to support migration of lymphocytes into diseased tissues. However, these molecules may be degraded by enzymes, a process that limits the influx of immune cells. For example, the chemokine CXCL10, which induces the recruitment of T lymphocytes into pathological tissues, is rapidly degraded by the enzyme dipeptidylpeptidase 4 (DPP4).
Researchers have previously shown that increased levels of DPP4 and the degraded form of CXCL10 in hepatitis C patients correlate with patients' inability to respond to interferon treatment. Following these results, the scientists predicted and have now confirmed that inhibiting this enzyme could improve the efficacy of immune responses, in particular antitumor responses.
The researchers showed that oral administration of a specific DPP4 inhibitor (sitagliptin) slows the development of several types of cancer in mice. In addition, the authors demonstrated that DPP4 inhibition increased the infiltration of T lymphocytes into tumors, and that the combination of this innovative treatment with existing immunotherapies eradicated the tumor.
Since health authorities have already approved DPP4 inhibitors for the treatment of type 2 diabetes, the conclusions drawn from these studies may quickly translate into clinical studies in humans. In fact, the researchers have already submitted a proposal for a phase I clinical trial, to evaluate the impact of sitagliptin treatment in patients with hepatocellular carcinoma.
Based on material originally posted by Institut Pasteur.