Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy (Nat Immunol 16:850, 2015)

報告日期: 2015/10/06
報告時間: 4:10/5:00
報告學生: 蔡逸成
講評老師: 楊倍昌
附件下載: 下載[1495-1443052732-1.pdf] 

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

Rosa Barreira da Silva1,2, Melissa E Laird1,2, Nader Yatim1,2, Laurence Fiette3,4, Molly A Ingersoll1,2 & Matthew L Albert1,2

Nature Immunology 16, 850–858 8 August, 2015

Abstract

When cancer occurred, the body induced a series of immune response to counter cancer cells.But this event evolved over time, the immune response gradually declinedin clinical immunotherapy. In this report the authors found that inhibiting Dipeptidylpeptidase 4 (DPP IV) enzyme activity could inducement lymphocyte trafficking by using DPP IV knockout mice or treatment of sitagliptin DPP VI inhibitor.In other words, the DPP IV suppressed that the immune response can be restored to original level and prevents cancer immune escape. In this research, the authors described most studies have ignored the importance of chemokine. The past studies have found that the DPP IV can truncate chemokine CXCL10 (Interferon g-induced protein 10) and inhibit this activity of chemokine. This condition lead that hepatitis B virus cannot enhance T-cell depletion(Charles and Dustin, 2011).Thereby, authors considerated whether chemokines, truncated by DPP4, lead inactivated, so that T cells cannot induced chemotaxis to sites of inflammation. This research found that treatment of C57BL/6 mice with sitagliptin (DPP IV inhibitor) protected chemokines untruncated, and induced more lymphocyte activation to destroy cancer cells. On the other hand,the authors induced melanoma mouse and treated them by using first-line drugs, anti-PD1 and anti-CTLA-4 combined with sitagilptin. There results found that therapeutic effect in this mode was very good.

Reference:

Charles, E.D., and Dustin, L.B. (2011). Chemokine antagonism in chronic hepatitis C virus infection. Journal of Clinical Investigation 121, 25-27.

da Silva, R.B., Laird, M.E., Yatim, N., Fiette, L., Ingersoll, M.A., and Albert, M.L. (2015). Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy. Nature Immunology 16, 850-+.