Skip to Main content Skip to Navigation
Journal articles

IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death.

Abstract : IRX-2 is a cytokine-based biologic agent that has the potential to enhance antitumor immune responses. We investigated whether IRX-2 can protect T cells from tumor-induced apoptosis. Tumor-derived microvesicles (MV) expressing FasL were purified from supernatants of tumor cells and incubated with activated CD8(+) T cells. MV induced significant CD8(+) T-cell apoptosis, as evidenced by Annexin binding (64.4+/-6.4%), caspase activation (58.1+/-7.6%), a loss of mitochondrial membrane potential (82.9+/-3.9%) and DNA fragmentation. T-cell pretreatment with IRX-2 prevented apoptosis. IRX-2-mediated cytoprotection was dose and time dependent and was comparable to effects of IL-2, IL-7 or IL-15. IRX-2 prevented MV-induced downregulation of JAK3 and TCRzeta chain and induced STAT5 activation in T cells. IRX-2 prevented MV-induced Bax and Bim upregulation (P<0.005-0.05), prevented cytochrome c release and Bid cleavage, and concurrently restored the expression of Bcl-2, Bcl-xL, FLIP and Mcl-1 (P<0.005-0.01) in T cells. In addition, IRX-2 reversed MV-induced inhibition of the PI3K/Akt pathway. An Akt inhibitor (Akti-1/2) abrogated protective effects of IRX-2, suggesting that Akt is a downstream target of IRX-2 signaling. Thus, ex vivo pretreatment of CD8(+) T cells with IRX-2 provided potent protection from tumor-induced apoptosis. IRX-2 application to future cancer biotherapies could improve their effectiveness by bolstering T-cell resistance to tumor-induced immunosuppression.
Document type :
Journal articles
Complete list of metadata

Cited literature [22 references]  Display  Hide  Download
Contributor : Ed. BMC Connect in order to contact the contributor
Submitted on : Wednesday, November 20, 2013 - 1:13:23 PM
Last modification on : Saturday, June 25, 2022 - 8:53:54 PM
Long-term archiving on: : Friday, February 21, 2014 - 4:29:05 AM





Christophe Legendre. IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death.. Cell Death and Differentiation, Nature Publishing Group, 2009, 16 (5), pp.708-18. ⟨10.1038/cdd.2008.197⟩. ⟨inserm-00906808⟩



Record views


Files downloads