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Nat Med. 2011 Aug 28;17(9):1094-100. doi: 10.1038/nm.2438.

Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido.

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1
Department of Surgery, Memorial Hospital, New York, New York, USA.

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(+) T cells and induced regulatory T cell (T(reg) 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.

PMID:
21873989
PMCID:
PMC3278279
DOI:
10.1038/nm.2438
[Indexed for MEDLINE]
Free PMC Article

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