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Retraction Free access | 10.1172/JCI81878

FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer

Stephanie K. Watkins, Ziqiang Zhu, Elena Riboldi, Kim A. Shafer-Weaver, Katherine E.R. Stagliano, Martha M. Sklavos, Stefan Ambs, Hideo Yagita, and Arthur A. Hurwitz

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Published May 1, 2015 - More info

Published in Volume 125, Issue 5 on May 1, 2015
J Clin Invest. 2015;125(5):2179–2179. https://doi.org/10.1172/JCI81878.
Copyright © 2015, American Society for Clinical Investigation
Published May 1, 2015 - Version history
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Related article:

FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer
Stephanie K. Watkins, … , Hideo Yagita, Arthur A. Hurwitz
Stephanie K. Watkins, … , Hideo Yagita, Arthur A. Hurwitz
Research Article

FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer

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Abstract

The limited success of cancer immunotherapy is often attributed to the loss of antigen-specific T cell function in situ. However, the mechanism for this loss of function is unknown. In this study, we describe a population of tumor-associated DCs (TADCs) in both human and mouse prostate cancer that tolerizes and induces suppressive activity in tumor-specific T cells. In tumors from human prostate cancer patients and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, TADCs expressed elevated levels of FOXO3 and Foxo3, respectively, which correlated with expression of suppressive genes that negatively regulate T cell function. Silencing FOXO3 and Foxo3 with siRNAs abrogated the ability of human and mouse TADCs, respectively, to tolerize and induce suppressive activity by T cells. Silencing Foxo3 in mouse TADCs was also associated with diminished expression of tolerogenic mediators, such as indoleamine-2,3-dioxygenase, arginase, and TGF-β, and upregulated expression of costimulatory molecules and proinflammatory cytokines. Importantly, transfer of tumor-specific CD4+ Th cells into TRAMP mice abrogated TADC tolerogenicity, which was associated with reduced Foxo3 expression. These findings demonstrate that FOXO3 may play a critical role in mediating TADC-induced immune suppression. Moreover, our results identify what we believe to be a novel target for preventing CTL tolerance and enhancing immune responses to cancer by modulating the immunosuppressive activity of TADCs found in the tumor microenvironment.

Authors

Stephanie K. Watkins, Ziqiang Zhu, Elena Riboldi, Kim A. Shafer-Weaver, Katherine E.R. Stagliano, Martha M. Sklavos, Stefan Ambs, Hideo Yagita, Arthur A. Hurwitz

×

Original citation: J Clin Invest. 2011;121(4):1361–1372. doi:10.1172/JCI44325.

Citation for this retraction: J Clin Invest. 2015;125(5):2179. doi:10.1172/JCI81878.

At the request of the corresponding author, the JCI is retracting the paper “FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer” based on findings of data falsification and fabrication regarding Figures 1D and 8A, likely data falsification regarding Figure 4A, likely falsification or fabrication regarding Figure 4B, and erroneous sample attribution in Table 1. Following extensive review by an NIH-appointed investigation committee, the NIH found that one author, Stephanie Watkins, was the sole individual responsible for the instances of research misconduct. None of the other authors was aware of the misconduct.

Footnotes

See the related article beginning on page 1361.

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