American Association for Cancer Research
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Supplementary Figure 2 from Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade

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journal contribution
posted on 2023-04-03, 23:06 authored by Ines Pires da Silva, Anne Gallois, Sonia Jimenez-Baranda, Shaukat Khan, Ana C. Anderson, Vijay K. Kuchroo, Iman Osman, Nina Bhardwaj

PDF file - 93K, Fig. S2. NK cells from melanoma patients down-regulate the expression of cytokine receptors, rendering them refractory to cytokine stimulation.



The immunoregulatory protein T-cell immunoglobulin- and mucin-domain–containing molecule-3 (Tim-3) mediates T-cell exhaustion and contributes to the suppression of immune responses in both viral infections and tumors. Tim-3 blockade reverses the exhausted phenotype of CD4+ and CD8+ T cells in several chronic diseases, including melanoma. Interestingly, natural killer (NK) cells constitutively express Tim-3; however, the role of Tim-3 in modulating the function of these innate effector cells remains unclear, particularly in human diseases. In this study, we compared the function of Tim-3 in NK cells from healthy donors and patients with metastatic melanoma. NK cells from the latter were functionally impaired/exhausted, and Tim-3 blockade reversed this exhausted phenotype. Moreover, Tim-3 expression levels were correlated with the stage of the disease and poor prognostic factors. These data indicate that Tim-3 can function as an NK-cell exhaustion marker in advanced melanoma and support the development of Tim-3–targeted therapies to restore antitumor immunity. Cancer Immunol Res; 2(5); 410–22. ©2014 AACR.

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