Non-redundant Requirement for CXCR3 Signaling during Tumoricidal T Cell Trafficking across Tumor Vascular Checkpoints

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Non-redundant Requirement for CXCR3 Signaling during Tumoricidal T Cell Trafficking across Tumor Vascular Checkpoints

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Title: Non-redundant Requirement for CXCR3 Signaling during Tumoricidal T Cell Trafficking across Tumor Vascular Checkpoints
Author: Mikucki, ME; Fisher, DT; Matsuzaki, J; Skitzki, JJ; Gaulin, NB; Muhitch, JB; Ku, AW; Frelinger, JG; Odunsi, K; Gajewski, TF; Luster, AD; Evans, SS

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Citation: Mikucki, M., D. Fisher, J. Matsuzaki, J. Skitzki, N. Gaulin, J. Muhitch, A. Ku, et al. 2015. “Non-redundant Requirement for CXCR3 Signaling during Tumoricidal T Cell Trafficking across Tumor Vascular Checkpoints.” Nature communications 6 (1): 7458. doi:10.1038/ncomms8458. http://dx.doi.org/10.1038/ncomms8458.
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Abstract: T cell trafficking at vascular sites has emerged as a key step in antitumor immunity. Chemokines are credited with guiding the multistep recruitment of CD8+ T cells across tumor vessels. However, the multiplicity of chemokines within tumors has obscured the contributions of individual chemokine receptor/chemokine pairs to this process. Moreover, recent studies have challenged whether T cells require chemokine receptor signaling at effector sites. Here, we investigate the hierarchy of chemokine receptor requirements during T cell trafficking to murine and human melanoma. These studies reveal a non-redundant role for GαI-coupled CXCR3 in stabilizing intravascular adhesion and extravasation of adoptively transferred CD8+ effectors that is indispensable for therapeutic efficacy. In contrast, functional CCR2 and CCR5 on CD8+ effectors fail to support trafficking despite the presence of intratumoral cognate chemokines. Taken together, these studies identify CXCR3-mediated trafficking at the tumor vascular interface as a critical checkpoint to effective T cell-based cancer immunotherapy.
Published Version: doi:10.1038/ncomms8458
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605273/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993537
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