IMMUNOSUPPRESSION IN CANCER PATIENTS

癌症患者的免疫抑制

基本信息

批准号：
3166607
负责人：
ARTHUR DALE BANKHURST
金额：
$ 13.49万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-01-01 至 1988-12-31
项目状态：
已结题

项目摘要

The overall aim of this proposal was to examine the mechanisms of impaired natural cytotoxicity mediated by natural killer (NK) cells in human diseases. A group of patients with colon and any other cancers was examined. The depressed NK activity was not related to the stage of the disease. The response of NK function to interferon (INF) was reduced in some of these patients. In addition, 40% of the patients had suppressive serum factors which were not either anti-lymphocyte antibodies or immune complexes. Some patients with systemic lupus erythematosus (SLE) also have a suppression of NK activity. The impaired NK activity in SLE did not appear to be related to a cell-mediated suppressive mechanism or to a depletion of effector cells. However, the release of natural killer cytotoxic factor (NKCF) was abnormal. The defective response of the NK cell to INF in SLE patients was found to be secondary, in part, to the presence of inhibitory serum factors and preactivation by INF. The inhibiting serum factors suppress NK function without evidence of lymphocyte cell death or inhibition of NK effector cell binding to tumor targets. The production of interleukin-2 (IL-2) and INF was normal in SLE patients so that the synthesis of these factors is not a major pathologic factor in the development of SLE. One aspect of OKM1+ cells was sheep erythrocyte positive (E+) while the others were not (E-). The OKM1+ E+ cells mediated more NK activity on a per cell basis than E-\OKM+ cells. In addition, the regulation of NK activity by neuropeptides (beta-endorphin and enkephalines) was examined. These neuropeptides increased the numbers of effector cell:tumor conjugates and the number of active killer cells among target-binding cells. Other studies have focused on suppressive cells associated with human immunodeficiency. We found, for example, that the major suppressor cell present in human cord blood is an OKT8+/lymphocyte. During the last year significant progress has been made concerning the regulation of NK activity in human diseases. The impairment of peripheral NK activity is not related to a decrease in the potential number of NK effector cells which bind target cells, but to an inhibition of activity due to multiple factors such as anti-lymphoid cell antibodies, immune aggregates, and other unidentified materials. In certain diseases, it appears that a relative refractoriness to enhancing factors such as INF may contribute to impaired NK activity. An important observation that neuropeptides such as beta-endorphin can influence NK activity was made. New observations concerning another type of cytotoxic cell, the so-called LAK cell, and its regulation by PG and factors produced by tumor cells may lead to important new data regarding the control of the LAK cell system and its relevance to the development of human cancers. (IS)

该提案的总体目的是检查受损的机制人类自然杀手（NK）细胞介导的天然细胞毒性疾病。一群结肠和任何其他癌症患者是检查。抑郁的NK活动与疾病。 NK功能对干扰素（INF）的响应减少了其中一些患者。此外，40％的患者抑制了不是抗淋巴细胞抗体或免疫的血清因子复合物。一些全身性红斑狼疮（SLE）的患者也有抑制NK活性。 SLE中的NK活动受损没有似乎与细胞介导的抑制机制有关或与效应细胞的消耗。但是，自然杀手的释放细胞毒性因子（NKCF）异常。 NK的缺陷响应发现SLE患者的细胞向INF的细胞是次要的，部分是 INF的抑制性血清因子的存在和预反应。这抑制血清因子抑制NK功能，而没有证据淋巴细胞细胞死亡或NK效应细胞与肿瘤结合的抑制目标。 SLE中的白介素2（IL-2）和INF的产生正常患者使这些因素的合成不是主要的病理 SLE发展的因素。 OKM1+细胞的一个方面是绵羊红细胞阳性（E+），而其他则不是（e-）。 OKM1+ E+ 与E- \ OKM+细胞相比，细胞以每个细胞为基础介导的NK活性更多。在补充，神经肽对NK活性的调节（β-内啡肽检查了Enkephalines）。这些神经肽增加了数量效应细胞：肿瘤结合物和活性杀伤细胞的数量在目标结合细胞中。其他研究的重点是抑制与人免疫缺陷相关的细胞。例如，我们发现人脐带血中存在的主要抑制细胞是 OKT8+/淋巴细胞。在过去的一年中，已经取得了重大进展调节人类疾病中NK活性。外围的损害 NK活性与NK潜在数量的减少无关效应细胞结合靶细胞，但会抑制活性由于多种因素，例如抗淋巴样细胞抗体，免疫聚集体和其他未识别的材料。在某些疾病中似乎对增强因素（例如INF）的相对难治性可能有助于NK活动受损。一个重要的观察结果 β-内啡肽等神经肽可以影响NK活性。有关另一种类型的细胞毒性细胞的新观察，所谓的 Lak细胞及其对PG的调节以及肿瘤细胞产生的因素可能导致有关Lak细胞系统控制和控制的重要新数据它与人类癌症的发展有关。（是）