CELLULAR FUNCTION AND IMMUNE THERAPY IN THE TREATMENT OF CANCER

“有效的免疫疗法的设计能够 根除化疗后残留的恶性细胞 依赖于对免疫和造血的了解 这一时期存在功能障碍。为此，我们有 检测癌症患者细胞功能的四个方面 治疗前和治疗后。首先，我们已经通过 大多数临床前动物模型和临床研究 出现在化疗后时期的CD4+T细胞被衍生 成人患者外周血中成熟T细胞由扩增而来。 从扩增中获得的T细胞数量后来下降 数量较多，容易发生细胞凋亡。两项临床研究表明 是基于这些结果发起的，目的是派生 最大化成人患者T细胞免疫活性的策略 接受化疗，并研究NK细胞生物学和 再生。细胞功能的第二个方面与细胞内 特定细胞因子T淋巴细胞群体的体外产生 表型：I型(Th1，Tc1)和II型(Th2，Tc2)。CD4+T细胞 Th1型细胞介导致死性移植物抗宿主病和移植物抗宿主病。在……里面 相比之下，CD8+细胞毒性T细胞分泌I型或II型 细胞因子被发现介导了强大的GVL效应，但减少了 GVHD。文化条件现在已经为 人类细胞因子定义的T细胞亚群的产生作为前奏 临床研究。这项工作的第三个方面涉及到 术后造血细胞亚群的变化 化疗。研究发现，化疗对人体健康造成损害 尽管有造血细胞因子，造血祖细胞仍然存在 心理治疗。这样的治疗刺激了阴性反应的产生。 造血调节剂。趋化因子Mig是新的 被确认为这样一个负面监管机构。这些结果产生了 T细胞再生和基因操作的意义 造血干细胞。工作的第四个方面集中在 抗原提呈细胞生物学。已有研究发现，细胞 单核/巨噬细胞系是树突状细胞的前体细胞，并且 钙离子载体对这类细胞的处理几乎激发了 均匀转化为树突状表型的细胞。应用程序 这些发现正在进行临床研究。

"The design of effective immune therapies to eradicate residual malignant cells following chemotherapy is dependent on understanding immune and hematopoietic dysfunctions present in this period. Toward this end, we have examined four facets of cellular function in patients with cancer before and after therapy. First, we have determined through preclinical animal models and clinical studies that the majority of CD4+ T cells present in the post-chemotherapy period are derived in adult patients from expansion of mature peripheral T cells. Population of T cells derived from expansion later decline in number and are susceptible to apoptosis. Two clinical studies have been initiated based on these results with the intent to derive strategies to maximize T cell immunocompetence in adult patients treated with chemotherapy and to investigate NK cell biology and regeneration. The second facet of cellular function concerns the in vitro generation of T lymphocyte populations of defined cytokine phenotype: Type I (Th1, Tc1) and Type II (Th2, Tc2). CD4+ T cells of Th1-type mediated both lethal GVHD and GVL. In contrast, CD8+ cytotoxic T cells secreting either Type I or Type II cytokines were found to mediate potent GVL effects with reduced GVHD. Culture conditions have now been established for the generation of human cytokine-defined T cell subsets as a prelude to clinical studies. The third facet of the work concerns characterizing alterations in hematopoietic cell populations following chemotherapy. It was found that chemotherapy damage to hematopoietic progenitors occurred despite hematopoietic cytokine therapy. Such treatment stimulated production of negative regulators of hematopoiesis. The chemokine Mig has been newly identified as one such negative regulator. These results have implications for T cell regeneration and for gene manipulation of hematopoietic stem cells. The fourth facet of the work has focused on antigen presenting cell biology. It has been found that cells of monocyte /macrophage lineage are precursors of dendritic cells, and that calcium ionophore treatment of such cells provokes almost uniform conversion to cells of dendritic phenotype. Application of these findings to clinical studies is in progress."