Mikucki, MEFisher, DTMatsuzaki, JSkitzki, JJGaulin, NBMuhitch, JBKu, AWFrelinger, JGOdunsi, KGajewski, TFLuster, ADEvans, SS2016-01-042015Mikucki, 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/ncomms8458.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993537T 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.en-USJournal Article2016-01-0410.1038/ncomms8458