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Tim-3 Regulation of Cancer Immunity

  • Kaori Sakuishi
  • Ana C. Anderson
Chapter

Abstract

Chronic unrelenting immune responses can lead to immunopathology that can be fatal. Consequently, the immune system has evolved both molecular and cellular mechanisms that serve to contract active immune responses and restore immune homeostasis. Molecular mechanisms include the upregulation of inhibitory or immune checkpoint receptors on T cells post activation. Cellular mechanisms include regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) that suppress active T-cell responses. Unfortunately, all of these mechanisms have been co-opted in cancer to suppress the generation of productive antitumor T-cell responses. In tumor-bearing hosts, the sustained expression of immune checkpoint receptors on T cells results in T-cell dysfunction or exhaustion. Moreover, MDSCs expand to large numbers in tumor-bearing hosts and the tumor microenvironment promotes Tregs. The inhibitory receptor T-cell immunoglobulin and mucin domain 3 (Tim-3) has a role in each of these mechanisms of immune suppression, thus highlighting the value of Tim-3 as a target for anticancer immunotherapy. Here, we discuss the role of Tim-3 in each of these mechanisms and the implications for the development of agents that target Tim-3 for cancer treatment.

Keywords

Regulatory T cells (Tregs) Checkpoint receptor T-cell exhaustion Immunotherapy 

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© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  1. 1.Center of Neurologic Diseases, Department of Neurology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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