Targeting Tim-3 and PD-1 Pathways to Reverse T Cell Exhaustion and Restore Anti-Tumor Immunity

Targeting Tim-3 and PD-1 Pathways to Reverse T Cell Exhaustion and Restore Anti-Tumor Immunity

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Targeting Tim-3 and PD-1 Pathways to Reverse T Cell Exhaustion and Restore Anti-Tumor Immunity

dc.contributor.author	Apetoh, Lionel
dc.contributor.author	Sullivan, Jenna M.
dc.contributor.author	Blazar, Bruce R.
dc.contributor.author	Sakuishi, Kaori
dc.contributor.author	Kuchroo, Vijay Kumar
dc.contributor.author	Anderson, Ana Carrizosa
dc.date.accessioned	2011-10-19T00:20:50Z
dc.date.issued	2010
dc.identifier.citation	Sakuishi, Kaori, Lionel Apetoh, Jenna M. Sullivan, Bruce R. Blazar, Vijay K. Kuchroo, and Ana C. Anderson. 2010. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. The Journal of Experimental Medicine 207(10): 2187-2194.	en_US
dc.identifier.issn	0022-1007	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:5265958
dc.description.abstract	The immune response plays an important role in staving off cancer; however, mechanisms of immunosuppression hinder productive anti-tumor immunity. T cell dysfunction or exhaustion in tumor-bearing hosts is one such mechanism. PD-1 has been identified as a marker of exhausted T cells in chronic disease states, and blockade of PD-1–PD-1L interactions has been shown to partially restore T cell function. We have found that T cell immunoglobulin mucin (Tim) 3 is expressed on CD8\(^+\) tumor-infiltrating lymphocytes (TILs) in mice bearing solid tumors. All Tim-3\(^+\) TILs coexpress PD-1, and Tim-3\(^+\)PD-1\(^+\) TILs repre- sent the predominant fraction of T cells infiltrating tumors. Tim-3\(^+\)PD-1\(^+\) TILs exhibit the most severe exhausted phenotype as defined by failure to proliferate and produce IL-2, TNF, and IFN-\(\gamma\). We further find that combined targeting of the Tim-3 and PD-1 pathways is more effective in controlling tumor growth than targeting either pathway alone.	en_US
dc.language.iso	en_US	en_US
dc.publisher	The Rockefeller University Press	en_US
dc.relation.isversionof	doi://10.1084/jem.20100643	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947065/pdf/	en_US
dash.license	LAA
dc.title	Targeting Tim-3 and PD-1 Pathways to Reverse T Cell Exhaustion and Restore Anti-Tumor Immunity	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	The Journal of Experimental Medicine	en_US
dash.depositing.author	Kuchroo, Vijay Kumar
dc.date.available	2011-10-19T00:20:50Z
dash.affiliation.other	HMS^Neurology-Brigham and Women's Hospital	en_US