医学
免疫学
白细胞介素2
淋巴因子激活杀伤细胞
细胞毒性T细胞
癌症研究
淋巴因子
癌症
细胞因子
T细胞
免疫系统
白细胞介素21
内科学
生物
体外
生物化学
出处
期刊:PubMed
日期:2000-04-01
卷期号:27 (2): 194-203
被引量:59
摘要
Interleukin-2 (IL-2) administered in pharmacologic doses to renal cancer patients with intact organ function and good performance status induces durable complete responses in about 5% of patients and partial responses in an additional 10% to 15%. The mechanism of antitumor efficacy of IL-2 is closely related to its ability to expand and activate cytotoxic lymphocytes of the natural killer (NK)- and thymic (T)-cell subsets that express IL-2 receptors (IL-2R). There is also accumulating evidence that local or generalized effector cell dysfunction, which is characteristic of patients with advanced cancer, can be reversed with IL-2 exposure. The toxicities of IL-2 are mediated by cytokines and other small molecules secreted by IL-2R-expressing cells responding to the binding of this ligand. The common mechanism for IL-2-induced multiorgan dysfunction appears to be a capillary leak syndrome directly mediated by local production of nitric oxide by cells of the monocyte-macrophage lineage. To date, efforts to improve on the antitumor activity of IL-2 by the addition of IL-2-activated peripheral blood mononuclear cells (lymphokine-activated killer [LAK] cells) or cell subsets selected for proximity or potential antigen-specificity (tumor-infiltrating lymphocytes [TIL]) have not led to improved therapeutic outcomes. Attempts to reduce the risks of IL-2 therapy (which could potentially allow for increased IL-2 administration) by blocking one or more of the known mediators of toxicity have also been disappointing. Current research is directed at developing combination regimens with additive or synergistic antitumor effects and incompletely overlapping toxicities, as well as the identification of tumor antigens that may be the target of more focused cellular therapies. The role of high-dose IL-2 in the adjuvant therapy of resected renal cancer at high risk of relapse is also under investigation.
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