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

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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

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