Abstract:
:Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8+ T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7). These CAL-101 T cells also persisted longer after transfer into tumor bearing mice in both the murine syngeneic and human xenograft mouse models. The less differentiated phenotype and improved engraftment of CAL-101 T cells resulted in stronger antitumor immunity compared to traditionally expanded CD8+ T cells in both tumor models. Thus, this report describes a novel direct enhancement of CD8+ T cells by a p110δ inhibitor that leads to markedly improved tumor regression. This finding has significant implications to improve outcomes from next generation cancer immunotherapies.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Bowers JS,Majchrzak K,Nelson MH,Aksoy BA,Wyatt MM,Smith AS,Bailey SR,Neal LR,Hammerbacher JE,Paulos CMdoi
10.3389/fimmu.2017.01221subject
Has Abstractpub_date
2017-09-29 00:00:00pages
1221issn
1664-3224journal_volume
8pub_type
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