Role of IL-2 in cancer immunotherapy: OncoImmunology: Vol 5, No 6 - 1 views
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IL-2 is one of the key cytokines with pleiotropic effects on the immune system
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approved for the treatment of metastatic renal cell carcinoma (1992) and later for metastatic melanoma (1998) by FDA
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It is produced predominately by antigen-simulated CD4+ T cells, while it can also be produced by CD8+ cells, natural killer (NK) cells, and activated dendritic cells (DC)
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It can promote CD8+ T-cell and NK cell cytotoxicity activity, and modulate T-cell differentiation programs in response to antigen, promoting naive CD4+ T-cell differentiation into T helper-1 (Th1) and T helper-2 (Th2) cells while inhibiting T helper-17 (Th17) differentiation
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Of note, Tregs, which act to dampen the immune response, constitutively express high levels of α chain
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IL-2Rα is unique to IL-2 and is expressed by a number of immune cells including T regulatory cells (Treg), activated CD4+ and CD8+T cells, B cells, mature DCs, endothelial cells
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Unfortunately, not all of patients would benefit from targeted therapy and nearly all patients who initially respond to targeted inhibitors inevitably develop acquired resistance to the treatment
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IL-2 also stimulates T-regulatory cells that constitutively express CTLA-4 and can suppress immune reactions. Hence, IL-2 might enhance antitumor reactivity in the presence of CTLA-4 blockade
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both HD and low-dose IL-2 therapy preferentially induce the expansion of CD4+CD25+Foxp3+ Treg and the Treg level remains elevated after each cycle of HD IL-2 therapy
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Due to rapid elimination and metabolism via the kidney, IL-2 has a short serum half-life of several minutes
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HD IL-2-induced severe toxicities including vascular leak syndrome (VLS), pulmonary edema, hypotension, and heart toxicities