Send to

Choose Destination
J Exp Med. 2010 Sep 27;207(10):2187-94. doi: 10.1084/jem.20100643. Epub 2010 Sep 6.

Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.

Author information

Center for Neurological Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Erratum in

  • J Exp Med. 2011 Jun 6;208(6):1331.


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 represent 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-γ. 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.

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms


Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center