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

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Balachandran, Vinod P, Cavnar, Michael J, Zeng, Shan, Bamboat, Zubin M, Ocuin, Lee M, Obaid, Hebroon, Sorenson, Eric C, Popow, Rachel, Ariyan, Charlotte, Rossi, Ferdinand, Besmer, Peter, Guo, Tianhua, Antonescu, Cristina R, Taguchi, Takahiro, Yuan, Jianda, Wolchok, Jedd D, Allison, James P, DeMatteo, Ronald P·2011·Nature Medicine

DOI 10.1038/nm.2438

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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 (Treg 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.

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See all 521

Authors: 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.
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 2011-08-28
Volume: 17
Issue: 9
Pages: 1094-1100
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/nm.2438
OpenAlex: W2106631163
Cited by: 521
References: 58
FWCI: 39.05
Type: journal article
Language: en
Open access: green

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

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