PI3K[delta] Is Essential for Tumor Clearance Mediated by Cytotoxic T Lymphocytes

PI3K[delta] is a lipid kinase of the phosphoinositide 3-kinase class 1A family and involved in early signaling events of leukocytes regulating proliferation, differentiation and survival. Currently, several inhibitors of PI3K[delta] are under investigation for the treatment of hematopoietic malignan...

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Bibliographic Details
Published inPloS one Vol. 7; no. 7; p. e40852
Main Authors Putz, Eva Maria, Prchal-Murphy, Michaela, Simma, Olivia Annabella, Forster, Florian, Koenig, Xaver, Stockinger, Hannes, Piekorz, Roland P, Freissmuth, Michael, Müller, Mathias, Sexl, Veronika, Zebedin-Brandl, Eva
Format Journal Article
LanguageEnglish
Published Public Library of Science 13.07.2012
Subjects
Cancer treatment
Colon cancer
Development and progression
T cells
Tumors
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Summary:PI3K[delta] is a lipid kinase of the phosphoinositide 3-kinase class 1A family and involved in early signaling events of leukocytes regulating proliferation, differentiation and survival. Currently, several inhibitors of PI3K[delta] are under investigation for the treatment of hematopoietic malignancies. In contrast to the beneficial effect of inhibiting PI3K[delta] in tumor cells, several studies reported the requirement of PI3K[delta] for the function of immune cells, such as natural killer and T helper cells. Cytotoxic T lymphocytes (CTLs) are essential for tumor surveillance. The scope of this study is to clarify the potential impact of PI3K[delta] inhibition on the function of CTLs with emphasis on tumor surveillance. Our results demonstrate that CTL-mediated tumor surveillance is severely impaired in the absence of PI3K[delta] and predict that impaired immunosurveillance may limit the effectiveness of PI3K[delta] inhibitors in long-term treatment.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0040852