TUMOR-DERIVED SOLUBLE IMMUNOREGULATORY FACTOR

肿瘤源性可溶性免疫调节因子

• 批准号: 3804720
• 负责人: B PACKARD
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3804720
• 关键词: cell cell interaction; cell communication molecule; cell growth regulation; cytokine; enzyme linked immunosorbent assay; gel filtration chromatography; growth media; immunoregulation; ion exchange chromatography; leukocyte activation /transformation; lymphocyte proliferation; mitogens; neoplasm /cancer immunology; neoplastic cell culture for noncancer research; neutralizing antibody; tissue /cell culture

This project was aimed at exploring the possible presence of soluble immunoreglatory factors of tumor origin. It was found that the presence of at least four irradiated, cultured human tumor cell lines could stimulate the proliferation of human lymphocytes; the observed proliferative stimulation was due to secreted factors as activity was present in the serum-free tumor cell supernatant (PNAS 87:4058-62, 1990). In addition, this supernatant has now been demonstrated to inhibit the proliferation of three human leukemic cell lines concomitantly with induction of differentiation. Immunologic and proliferative assays using ELLISAs, neutralizing antibodies, and recombinant standards indicated nonidentity of at least one secreted factor with any previously characterized cytokine. A factor with unique biophysical and biochemical properties which has now been purified by a combination of ion exchange, gel filtration, and hydrophobic interaction chromatography is currently being sequenced. Identification of secreted factor(s) from tumor cells as a source of mitogenic activity for lymphocytes and myeloid differentiation induction supports the idea that the tumor immunoenvironment as recognized by immunocytes is defined by soluble mediators in addition to the well- studied cell-cell contact interactions.

这个项目的目的是探索可能存在的可溶性 肿瘤起源的免疫调节因素。人们发现，这种存在 至少四个受辐射的培养的人类肿瘤细胞株可以 刺激人类淋巴细胞的增殖；观察到 增殖刺激是由于分泌因子，因为活性是 存在于无血清肿瘤细胞上清液中(PNAS 87：4058-62,1990)。 此外，这种上清液现在已经被证明可以抑制 三种人白血病细胞系同时增殖的研究 诱导分化。 使用ELLISA的免疫学和增殖学分析，中和 抗体和重组标准表明至少不同 一种分泌因子与任何先前描述的细胞因子。一个因素 具有独特的生物物理和生化特性，现在已经 通过离子交换、凝胶过滤和疏水相结合进行纯化 目前正在对相互作用层析进行测序。 肿瘤细胞分泌因子(S)作为肿瘤来源的鉴定 淋巴细胞有丝分裂活性与髓系诱导分化 支持这样的观点，即肿瘤免疫环境由 免疫细胞是由可溶介质定义的，除了良好的- 研究了细胞-细胞接触相互作用。