Mechanisms of tumor-induced immunosuppression: Evidence for contact-dependent T cell suppression by monocytes
Mechanisms of tumor-induced immunosuppression: Evidence for contact-dependent T cell suppression by monocytes
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DOI：
10.1007/bf03401653
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发表时间：
1996-11-01
影响因子：
5.7
通讯作者：
Nabel, GJ
中科院分区：
文献类型：
--
作者：
Jaffe, ML;Arai, H;Nabel, GJ
背景：小鼠肿瘤的进行性生长伴随着特异性T细胞应答的下调。这种抑制所涉及的因素尚未完全了解。在这里，我们已经开发了一个模型来检查宿主免疫效应细胞在抑制T细胞功能中的作用。在这个模型中，进行性生长的结肠癌细胞系，CT 26，是伴随着损失的T细胞对同种异体抗原的细胞溶解和增殖assays.Materials和方法：CT 26肿瘤接种到BALB/c同基因小鼠。肿瘤生长，细胞溶解性T细胞反应，淋巴细胞增殖，流式细胞仪分析进行了荷瘤动物肿瘤inoculation.Results后7或28天：从荷瘤小鼠脾细胞被发现抑制正常小鼠脾细胞对同种异体抗原的增殖反应。通过FAGS分析对脾细胞群的检查显示单核细胞百分比增加，如通过Mac-1抗原CD 11b的表达所定义的。从荷瘤宿主脾脏中去除Mac-1阳性细胞可缓解荷瘤小鼠脾细胞对同种异体抗原的增殖反应的抑制，而添加Mac-1阳性富集细胞可抑制正常T细胞对同种异体抗原的增殖反应。细胞接触需要这种inhibition.Conclusions：抑制性单核细胞的肿瘤诱导中起着重要的作用，在一般的免疫抑制动物携带CT 26肿瘤。鉴定这种作用的机制和逆转肿瘤诱导的巨噬细胞抑制可能有助于开发有效的恶性肿瘤免疫疗法。
Background: The progressive growth of tumors in mice is accompanied by down-regulation of specific T cell responses. The factors involved in this suppression are not completely understood. Here, we have developed a model to examine the role of host immune effector cells in the inhibition of T cell function. In this model, progressive growth of a colon carcinoma line, CT26, is accompanied by loss of T cell response to alloantigens in both cytolytic and proliferation assays.Materials and Methods: The CT26 tumor was inoculated into BALB/c syngeneic mice. Tumor growth, cytolytic T cell responses, lymphocyte proliferation, and flow cytometric analysis was performed in rumor-bearing animals 7 or 28 days after tumor inoculation.Results: Spleen cells from tumor-bearing mice were found to suppress the proliferative response of spleen cells from normal mice to alloantigens. Examination of the spleen cell population by FAGS analysis revealed an increase in the percentage of monocytes as defined by expression of CD11b, the Mac-1 antigen. Removal of the Mac-1-positive cells from the tumor-bearing hosts spleen relieved suppression of the tumor-bearing mouse spleen cell proliferative response to alloantigens, and addition of the Mac-1-positive enriched cells suppressed proliferation of normal T cells in response to alloantigens. Cell contact was required for this inhibition.Conclusions: Tumor induction of suppressive monocytes plays an important role in the general immunosuppression noted in animals bearing CT26 tumors. Identification of the mechanisms responsible for this effect and reversal of tumor-induced macrophage suppression may facilitate efforts to develop effective immunotherapy for malignancy.