Rosa Barreira da Silva and her colleagues employed means to inhibit the activity of dipeptidylpeptidase 4 (DPP4), an enzyme that degrades small molecules called chemokines, important to induce the cell migration. The authors showed that oral administration of a specific DPP4 inhibitor (sitagliptin) slows the development of several types of cancer in mice, restoring naturally occurring tumor immunity. In addition, the authors demonstrated that DPP4 inhibition prevented the degradation of the chemokine CXCL10, increasing the infiltration of T lymphocytes into tumors; and that the combination of this innovative treatment with existing immunotherapies (such as checkpoint blockade) eradicated the tumor.
Rosa Barreira da Silva is a postdoctoral researcher at the Laboratory of Dendritic Cell Immunobiology, a mixed Pasteur/Inserm unit headed by Matthew Albert at the Institut Pasteur, Paris, France. This project has received funding from the Pasteur-Roux grant, the French Cancer League (Ligue Contre le Cancer), the Fondation ARC cancer research organization and the French National Research Agency (ANR) as part of the "Immuno-Onco" LabEx (Laboratories of Excellence) program.
Rosa Barreira da Silva,Melissa E Laird, Nader Yatim, Laurence Fiette, Molly A Ingersoll & Matthew L Albert. “Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy”, Nature Immunology, doi:10.1038/ni.3201, June 15, 2015