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- W4362546221 abstract "<div>Abstract<p>The Wnt/β-catenin pathway regulates T-cell functions, including the repression of effector functions to the advantage of memory development via Tcf1. In a companion study, we demonstrate that, in human cancers, Wnt3a/β-catenin signaling maintains tumor-infiltrating T cells in a partially exhausted status. Here, we have investigated the effects of Wnt3a neutralization <i>in vivo</i> in a mouse tumor model. Abundant Wnt3a was released, mostly by stromal cells, in the tumor microenvironment. We tested whether Wnt3a neutralization <i>in vivo</i> could rescue the effector capacity of tumor-infiltrating T cells, by administering an antibody to Wnt3a to tumor-bearing mice. This therapy restrained tumor growth and favored the expansion of tumor antigen–specific CD8<sup>+</sup> effector memory T cells with increased expression of Tbet and IFNγ and reduced expression of Tcf1. However, the effect was not attributable to the interruption of T-cell–intrinsic β-catenin signaling, because Wnt3a/β-catenin activation correlated with enhanced, not reduced, T-cell effector functions both <i>ex vivo</i> and <i>in vitro</i>. Adoptively transferred CD8<sup>+</sup> T cells, not directly exposed to the anti-Wnt3a antibody but infiltrating previously Wnt3a-neutralized tumors, also showed improved functions. The rescue of T-cell response was thus secondary to T-cell–extrinsic changes that likely involved dendritic cells. Indeed, tumor-derived Wnt3a strongly suppressed dendritic cell maturation <i>in vitro</i>, and anti-Wnt3a treatment rescued dendritic cell activities <i>in vivo</i>. Our results clarify the function of the Wnt3a/β-catenin pathway in antitumor effector T cells and suggest that Wnt3a neutralization might be a promising immunotherapy for rescuing dendritic cell activities. <i>Cancer Immunol Res; 6(8); 953–64. ©2018 AACR</i>.</p></div>" @default.
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- W4362546221 date "2023-04-03" @default.
- W4362546221 modified "2023-09-24" @default.
- W4362546221 title "Data from Wnt3a Neutralization Enhances T-cell Responses through Indirect Mechanisms and Restrains Tumor Growth" @default.
- W4362546221 doi "https://doi.org/10.1158/2326-6066.c.6549131.v1" @default.
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