Tim-3: An Emerging Target in the Cancer Immunotherapy Landscape

Abstract

The cancer immunotherapy field has grown exponentially in the past few years, largely driven by the success of immune checkpoint blockade. Therapies targeting the immune checkpoint molecules CTLA-4 and PD-1 have achieved objective responses in melanoma, renal cancer, and lung cancer; however, a large number of patients are still suffering with these cancers that are not benefiting from these therapies. Moreover, several cancers have proved to be largely refractory to therapies that target CTLA-4 and PD-1. This has catalyzed interest in targeting novel immune checkpoint receptors with the goal of realizing the full potential of checkpoint blockade for treating cancer. In this regard, the immune checkpoint receptor Tim-3 exhibits several unique features that make it an intriguing candidate for the next wave of therapies that target immune checkpoints in cancer. Cancer Immunol Res; 2(5); 393-8. Ó2014 AACR.

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

“…Tim-3, one of the most important members of this family, is primarily expressed in CD8 + T cells, monocytes, dendritic cells, and mast cells. Tim-3 is a specific surface marker of Th1 cells, and regulates autoimmune and allergic disease by mediating the immune response of Th1 cells (Han et al, 2013;Anderson, 2014). Furthermore, Tim-3 was found to be closely related to the occurrence and development of several types of cancer, including prostate cancer, non-small cell cancer, cervical cancer, and melanoma (Geng et al, 2006;Cao et al, 2013).…”

Tumor antigen-targeting monoclonal antibody-based immunotherapy: Orchestrating combined strategies for the development of long-term antitumor immunity

“…51 These interesting observations raise the question of whether antibodies/ inhibitors targeting CTLA4, PD-1/PD-L1, Tim3 or other inhibitory checkpoints might also increase the therapeutic efficacy of TA-targeting mAb-based immunotherapy. To our knowledge only one study suggests that it might be the case.…”

Aptamer-Targeted Attenuation of IL-2 Signaling in CD8 + T Cells Enhances Antitumor Immunity

“…Tim-3 expression on Tregs marks highly suppressive effector Tregs. 17 The mean differences among the groups, as shown in Figure 5, have not reached statisical significance because of the large intragroup variability, commonly seen when measuring tumor infiltration of lymphocytic subsets. Nonetheless, consistent with the tumor inhibition studies (Figure 4B), these observations suggest that 4-1BB-targeted downregulation of CD25 enhances the immunogenicity of irradiated tumors in mice.…”

“…17 Radiation led to a small reduction of CD4 + T cells in the tumor and both Foxp3 negative conventional T cells (Tconvs) ( Figure 5D) and Foxp3-expressing regulatory T cells (Tregs) (Figure 5E), which was prevented by treatment with 4-1BB-CD25 conjugate. The tumor-infiltrating Tregs from mice co-treated with radiation and 4-1BB-CD25, but not 4-1BB-luc, exhibited a reduced activation status, as measured by Tim-3 ( Figure 5I) and KLRG-1 expression ( Figure 5H).…”