Ujhazy Peter, Zaleskis Gintaras, Mihich Enrico, Ehrke M Jane, Berleth Erica S
Department of Pharmacology and Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Cancer Immunol Immunother. 2003 Jul;52(7):463-72. doi: 10.1007/s00262-003-0391-x. Epub 2003 Apr 16.
To examine the basis of the immune modulation induced by the anticancer agent doxorubicin (DOX), the immunophenotype, tumoricidal activity, cytokine protein and mRNA expression were determined using peritoneal exudate cells (PEC) from saline-treated (untreated) and DOX-treated mice. A greater percentage of PEC from DOX-treated mice than from untreated mice were adherent to plastic, had characteristics of granulocytes, and were positive for the NK1.1, CD11b/Mac-1, and CD3 markers. DOX decreased the percentage of CD45R/B220+ cells. PEC from DOX-treated mice had greater tumoricidal potential than those from untreated mice since IL2, LPS, or IFNgamma alone increased the cytolytic activity of PEC from DOX-treated mice, whereas PEC from untreated mice required both LPS and IFNgamma to become cytolytic. DOX treatment modulated the expression of specific cytokines. Following stimulation in culture, PEC from DOX-treated mice produced more TNF, IL1, and IFNgamma than PEC from untreated mice. DOX treatment increased the levels of TNF, but not IL1, mRNA and decreased the levels of IL6 mRNA and protein. These data demonstrate that a single DOX injection induces specific effects in PEC and, as a consequence, increases the tumoricidal potential of cells of the macrophage and natural killer types.
为了研究抗癌药物阿霉素（DOX）诱导免疫调节的基础，我们使用来自生理盐水处理（未处理）和DOX处理小鼠的腹腔渗出细胞（PEC）来测定免疫表型、杀肿瘤活性、细胞因子蛋白和mRNA表达。与未处理小鼠相比，DOX处理小鼠的PEC中更大比例的细胞能黏附于塑料表面，具有粒细胞特征，并且NK1.1、CD11b/Mac-1和CD3标记呈阳性。DOX降低了CD45R/B220+细胞的百分比。DOX处理小鼠的PEC比未处理小鼠的PEC具有更强的杀肿瘤潜力，因为单独的IL2、LPS或IFNγ就能增强DOX处理小鼠PEC的细胞溶解活性，而未处理小鼠的PEC需要LPS和IFNγ两者才能具有细胞溶解活性。DOX处理调节了特定细胞因子的表达。在培养中受到刺激后，DOX处理小鼠的PEC比未处理小鼠的PEC产生更多的TNF、IL1和IFNγ。DOX处理增加了TNF的水平，但未增加IL1的水平，同时降低了IL6 mRNA和蛋白的水平。这些数据表明，单次注射DOX会在PEC中诱导特定效应，从而增加巨噬细胞和自然杀伤细胞类型细胞的杀肿瘤潜力。
