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
| Title: | Targeting Tim-3 and PD-1 Pathways to Reverse T Cell Exhaustion and Restore Anti-Tumor Immunity |
| Author: |
Apetoh, Lionel; Sullivan, Jenna M.; Blazar, Bruce R.; Sakuishi, Kaori; Kuchroo, Vijay Kumar; Anderson, Ana Carrizosa
Note: Order does not necessarily reflect citation order of authors. |
| 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. |
| Full Text & Related Files: |
2947065.pdf (1.357Mb; PDF) 
|
| 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. |
| Published Version: | doi://10.1084/jem.20100643 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947065/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:5265958 |
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