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Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido.
- Source :
- Nature Medicine; Sep2011, Vol. 17 Issue 9, p1094-1100, 7p, 6 Graphs
- Publication Year :
- 2011
-
Abstract
- Imatinib mesylate targets mutated KIT oncoproteins in gastrointestinal stromal tumor (GIST) and produces a clinical response in 80% of patients. The mechanism is believed to depend predominantly on the inhibition of KIT-driven signals for tumor-cell survival and proliferation. Using a mouse model of spontaneous GIST, we found that the immune system contributes substantially to the antitumor effects of imatinib. Imatinib therapy activated CD8<superscript>+</superscript> T cells and induced regulatory T cell (T<subscript>reg</subscript> cell) apoptosis within the tumor by reducing tumor-cell expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido). Concurrent immunotherapy augmented the efficacy of imatinib in mouse GIST. In freshly obtained human GIST specimens, the T cell profile correlated with imatinib sensitivity and IDO expression. Thus, T cells are crucial to the antitumor effects of imatinib in GIST, and concomitant immunotherapy may further improve outcomes in human cancers treated with targeted agents. [ABSTRACT FROM AUTHOR]
- Subjects :
- IMATINIB
GASTROINTESTINAL tumors
T cells
CELL proliferation
LABORATORY mice
APOPTOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 17
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 65526083
- Full Text :
- https://doi.org/10.1038/nm.2438