Jiang, YLi, YZhu, B2016-01-042015Jiang, Y, Y Li, and B Zhu. 2015. “T-cell exhaustion in the tumor microenvironment.” Cell Death & Disease 6 (6): e1792. doi:10.1038/cddis.2015.162. http://dx.doi.org/10.1038/cddis.2015.162.2041-4889http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993513T-cell exhaustion was originally identified during chronic infection in mice, and was subsequently observed in humans with cancer. The exhausted T cells in the tumor microenvironment show overexpressed inhibitory receptors, decreased effector cytokine production and cytolytic activity, leading to the failure of cancer elimination. Restoring exhausted T cells represents an inspiring strategy for cancer treatment, which has yielded promising results and become a significant breakthrough in the cancer immunotherapy. In this review, we overview the updated understanding on the exhausted T cells in cancer and their potential regulatory mechanisms and discuss current therapeutic interventions targeting exhausted T cells in clinical trials.en-USJournal Article2016-01-0410.1038/cddis.2015.162