TUMOR-DERIVED MITOGENIC ACTIVITY FOR TUMOR-INFILTRATING LYMPHOCYTES

肿瘤浸润性淋巴细胞的肿瘤衍生有丝分裂活性

• 批准号: 3811177
• 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/3811177
• 关键词: cell cell interaction; cytotoxic T lymphocyte; interleukin 2; killer cells; leukocyte activation /transformation; lymphocyte; lymphokines; melanoma; mitogens; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; tissue /cell culture

The idea that the tumor environment is intrinsically immunogenic and therefore contains lymphocytes with the potential to induce tumor regressio has led to the use of tumor infiltrating lymphocytes (TILS) in clinical trials. In this procedure lymphocytes are grown ex vivo directly from tumor in the presence of the lymphokine interleukin 2 (IL-2); patients are reinfused with their TILs after the latter have been expanded in culture fo several weeks. Although TILs have shown in vivo efficacy, the characteristics of the tumor environment which result in the existence of TILs in vivo remain unclear. Two classes of stimuli -- one derived from cell-cell contact between tumor cells and immunocytes and the other from soluble factors secreted by tumor cells with receptors for them embedded in immunocyte plasma membranes -- are believed to influence T-cell homing and proliferation. Although IL-2 is a potent mitogen for T-cells (the phenotype of TILs), its biosynthesis is mainly confined to immunocytes. In this study the subject of soluble factors other than IL-2 secreted by tumor cell lines as sources of stimuli for TIL proliferation is being addressed. As a starting point for this work, the issue of whether a tumor cell line established from a melanoma tumor could stimulate the growth of TILs derive from melanoma masses was examined. After confirming the amplification potential of three melanoma cell lines, a nonmelanoma line was tested for the same bioactivity and found to be at least as potent a mitogenic source. Mitogenic activity for TILs was found in supernatants from both melanoma an nonmelanoma supernatants; hence, tumor-derived mitogenic activity for TILs could be ascribed to secreted factors. Biochemical and biophysical studies are underway to identify and characterize tumor-derived mitogenic factors for TILS.

认为肿瘤环境具有内在的免疫原性和 因此含有有可能诱导肿瘤消退的淋巴细胞 已导致肿瘤浸润性淋巴细胞(TIL)在临床上的使用 审判。在这个过程中，淋巴细胞是直接从肿瘤体外培养出来的。 在淋巴因子白介素2(IL-2)存在的情况下；患者 在后者扩大培养后再灌流他们的TIL 几个星期。尽管TIL已经显示出体内的疗效，但 导致肿瘤存在的肿瘤环境的特征 体内的TIL仍不清楚。两类刺激--一类来自 肿瘤细胞与免疫细胞之间的细胞-细胞接触 肿瘤细胞分泌的可溶性因子及其受体 免疫细胞质膜被认为影响T细胞归巢和 扩散。尽管IL-2是一种强大的T细胞有丝分裂原(表型 TIL)，其生物合成主要局限于免疫细胞。在这项研究中 肿瘤细胞系分泌IL-2以外的可溶性因子的研究 作为TIL扩散的刺激来源的问题正在得到解决。作为一名 这项工作的起点，是肿瘤细胞系是否 从黑色素瘤建立可以刺激TIL来源的生长 对黑色素瘤肿块进行检查。确认扩增后 三种黑色素瘤细胞系的潜能，一种非黑色素瘤细胞系被测试 同样的生物活性，并被发现至少是一个有效的有丝分裂来源。 在黑色素瘤和黑色素瘤的培养上清液中均发现TIL的有丝分裂活性 非黑色素瘤上清液；因此，肿瘤来源的TIL有丝分裂活性 可能归因于分泌因素。生化和生物物理研究 正在鉴定和表征肿瘤来源的有丝分裂因子 用于TILs。