Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido.
Publication/Presentation Date
8-28-2011
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(+) 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.
Volume
17
Issue
9
First Page
1094
Last Page
1100
ISSN
1546-170X
Published In/Presented At
Balachandran, V. P., Cavnar, M. J., Zeng, S., Bamboat, Z. M., Ocuin, L. M., Obaid, H., Sorenson, E. C., Popow, R., Ariyan, C., Rossi, F., Besmer, P., Guo, T., Antonescu, C. R., Taguchi, T., Yuan, J., Wolchok, J. D., Allison, J. P., & DeMatteo, R. P. (2011). Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido. Nature medicine, 17(9), 1094–1100. https://doi.org/10.1038/nm.2438
Disciplines
Medicine and Health Sciences
PubMedID
21873989
Department(s)
Department of Surgery, Lehigh Valley Topper Cancer Institute
Document Type
Article