IN SITU ANTITUMOR IMMUNITY AND EFFECTS OF RADIATION

这项研究的目的是了解发生的相互作用 恶性细胞和宿主免疫系统细胞之间的相互作用， 确定实体肿瘤和治疗中的微环境条件 例如辐射可以改变这些相互作用。 产生有效 抗肿瘤免疫需要免疫细胞，如特异性溶细胞因子， T淋巴细胞（CTL）接受足够的抗原刺激，迁移并 外渗到肿瘤部位，一旦有能够发挥作用， 肿瘤内的情况。 这些条件，特别是 在肿瘤内发现的缺氧是相当令人感兴趣的，因为 缺氧可对治疗方式具有剂量改变作用，特别是 放疗，但也可能化疗，也许免疫疗法。 缺氧在限制性脑缺血中作用的实验和临床研究 由于缺乏可靠的技术， 以所需的分辨率水平识别和量化缺氧细胞。 我们最近开发了针对一种新的 硝基咪唑化合物， 2-（2-硝基-1H-咪唑-1基）-N-（2，2，3，3，3-五氟丙基）乙酰胺或 EF 5，选择性地结合gypoprotein细胞，现在允许准确的评估 在单细胞水平上肿瘤内缺氧的程度。 在这 建议，我们将确定细胞因子是如何产生的恶性和 肿瘤局部微环境中的宿主细胞影响1） 免疫细胞的功能和2）肿瘤内的微环境。 我们推测，实体瘤内的缺氧条件可能限制了肿瘤的生长。 免疫活性宿主细胞的浸润和功能， 细胞因子可以改变缺氧的水平。 我们将探索缺氧 肿瘤内的条件影响粘附分子在 血管内皮细胞和肿瘤细胞本身。 的影响 放疗对肿瘤内细胞因子产生和粘附的影响 分子表达也将被研究，以提供必要的信息 恶性疾病的最佳治疗方法。

The purpose of this research is to understand the interactions that occur between malignant cells and cells of the host immune system, and to determine how microenvironment conditions within solid tumors and therapies such as radiation may alter these interactions. Generation of effective anti-tumor immunity requires that immune cells, such as specific cytolytic T lymphocytes (CTL), receive adequate antigenic stimulation, migrate and extravasate into the tumor site, and once there be able to function under the conditions present within the tumor. These conditions, particularly they hypoxia found within tumors are of considerable interest, because hypoxia can hava dose modifying effect on therapy modalities, particularly radiotherapy, but probably also chemotherapy and perhaps immunotherapy. Experimental and clinical studies on the role o hypoxia in limiting treatment efficacy have been limited by the lack of a reliable technique to identify and quantify hypoxic cells at the level of resolution needed. Our recent development of monoclonal antibodies against a new nitroimidazole compound, 2-(2-nitro-1H-imidazol-1yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide or EF5, that selectively binds gypoxic cells now allows an acurate assessment of the extend of hypoxia within tumors at the single cell level. In this proposal, we will determine how cytokines produced by both malignant and host cells within the local microenvironment of tumors affect 1) the function of immune cells and 2) the microenvironment within the tumors. We hypothesize that hypoxic conditions within solid tumors may limit the infiltration and function of immunologically active host cells and that cytokines can alter the level of hypoxia. We will explore how hypoxic conditions within tumors affect expression of adhesion molecules on vascular endothelial cells and on the tumor cells themselves. The effects of radiotherapy on both cytokine production within tumors and on adhesion molecule expression will also be studied to provide information essential for the optimal treatment of malignant disease.