Non-redundant Requirement for CXCR3 Signaling during Tumoricidal T Cell Trafficking across Tumor Vascular Checkpoints
DSpace/Manakin Repository
Non-redundant Requirement for CXCR3 Signaling during Tumoricidal T Cell Trafficking across Tumor Vascular Checkpoints
| 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
Note: Order does not necessarily reflect citation order of authors. |
| 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. |
| Full Text & Related Files: |
4605273.pdf (1.358Mb; PDF) 
|
| 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 |
| Downloads of this work: |
This item appears in the following Collection(s)
-
HMS Scholarly Articles [20560]
Contact administrator regarding this item (to report mistakes or request changes)
