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© Research
Publication : Nature immunology

Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature immunology - 15 Jun 2015

Barreira da Silva R, Laird ME, Yatim N, Fiette L, Ingersoll MA, Albert ML

Link to Pubmed [PMID] – 26075911

Nat. Immunol. 2015 Aug;16(8):850-8

The success of antitumor immune responses depends on the infiltration of solid tumors by effector T cells, a process guided by chemokines. Here we show that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10 and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide direct in vivo evidence for control of lymphocyte trafficking via CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing biologically active forms of chemokines as a strategy to enhance tumor immunotherapy.

http://www.ncbi.nlm.nih.gov/pubmed/26075911