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Corrigendum Open Access | 10.1172/jci.insight.145847

MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity

Alisa B. Lee-Sherick, Kristen M. Jacobsen, Curtis J. Henry, Madeline G. Huey, Rebecca E. Parker, Lauren S. Page, Amanda A. Hill, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Craig T. Jordan, Deborah DeRyckere, and Douglas K. Graham

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Published December 3, 2020 - More info

Published in Volume 5, Issue 23 on December 3, 2020
JCI Insight. 2020;5(23):e145847. https://doi.org/10.1172/jci.insight.145847.
© 2020 axis et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 3, 2020 - Version history
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MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity
Alisa B. Lee-Sherick, … , Deborah DeRyckere, Douglas K. Graham
Alisa B. Lee-Sherick, … , Deborah DeRyckere, Douglas K. Graham
Inhibition of MERTK in acute lymphoblastic leukemia models has direct therapeutic effects on leukemia cells and induces antitumor immunity via suppression of the coinhibitory PD-1 axis.
Research Article Oncology Therapeutics

MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity

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Abstract

MERTK is ectopically expressed and promotes survival in acute lymphoblastic leukemia (ALL) cells and is thus a potential therapeutic target. Here we demonstrate both direct therapeutic effects of MERTK inhibition on leukemia cells and induction of anti-leukemia immunity via suppression of the coinhibitory PD-1 axis. A MERTK-selective tyrosine kinase inhibitor, MRX-2843, mediated therapeutic anti-leukemia effects in immunocompromised mice bearing a MERTK-expressing human leukemia xenograft. In addition, inhibition of host MERTK by genetic deletion (Mertk–/– mice) or treatment with MRX-2843 significantly decreased tumor burden and prolonged survival in immune-competent mice inoculated with a MERTK-negative ALL, suggesting immune-mediated therapeutic activity. In this context, MERTK inhibition led to significant decreases in expression of the coinhibitory ligands PD-L1 and PD-L2 on CD11b+ monocytes/macrophages in the leukemia microenvironment. Furthermore, although T cells do not express MERTK, inhibition of MERTK indirectly decreased PD-1 expression on CD4+ and CD8+ T cells and decreased the incidence of splenic FOXP3+ Tregs at sites of leukemic infiltration, leading to increased T cell activation. These data demonstrate direct and immune-mediated therapeutic activities in response to MERTK inhibition in ALL models and provide validation of a translational agent targeting MERTK for modulation of tumor immunity.

Authors

Alisa B. Lee-Sherick, Kristen M. Jacobsen, Curtis J. Henry, Madeline G. Huey, Rebecca E. Parker, Lauren S. Page, Amanda A. Hill, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Craig T. Jordan, Deborah DeRyckere, Douglas K. Graham

×

Original citation: JCI Insight. 2018;3(21):e97941. https://doi.org/10.1172/jci.insight.97941

Citation for this corrigendum: JCI Insight. 2020;5(23):e145847. https://doi.org/10.1172/jci.insight.145847

The graph shown in Figure 6D was inadvertently duplicated in Figure 6B. However, the data shown in Figure 6 were correctly analyzed and statistics remain as published. The corrected Figure 6 is below. The article has been updated with the corrected information.

Figure 6

The authors regret the error.

Footnotes

See the related article at MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity.

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