Characterization of Tumor Specific T Cells in Melanoma

描述：(申请人摘要)这项建议的目标是在中国学习 详述肿瘤相关特异性T细胞的生物学特性 新生(目标1)或疫苗接种后(目标2)出现的抗原(TAA) 黑色素瘤患者。使用功能强大的新工具，如多肽/MHC 四聚体和10色流式细胞仪分析，我们将评估高达45的表达 表面和细胞内标记物、细胞因子表达和功能状态 直接从黑色素瘤患者身上分离的TAA特异性T细胞。我们还将 确定这类细胞的基因表达谱(目标3)以阐明 功能和功能异常的TAA特异性T细胞的分子差异 人口。通过将这些数据与患者的临床状态相关联 从每个人群中分离出来的结果和最终的临床结果，我们 希望了解为什么TAA特异性T细胞对某些患者具有保护作用 在其他人身上就不是了。最后，我们将剖析T细胞的调节因素 通过测试不同个体和组合的癌症功能障碍 诱导或逆转T细胞功能障碍的免疫调节剂(目标4)。 总而言之，这些数据应该会让我们更好地理解 T细胞对黑色素瘤的反应，并可能导致当前癌症的改善 免疫疗法即将到来。

DESCRIPTION: (Applicant's Abstract) The goal of this proposal is to study in detail the biological properties of T cells specific for tumor-associated antigens (TAAs) that arise either de novo (Aim 1) or postvaccination (Aim 2) in patients with melanoma. Using powerful and novel tools such as peptide/MHC tetramers and 10-color FACS analysis, we will assess the expression of up to 45 surface and intracellular markers, cytokine expression, and functional status of TAA-specific T cells isolated directly from melanoma patients. We will also determine the gene expression profiles of such cells (Aim 3) to elucidate the molecular differences between functional and dysfunctional TAA-specific T cell populations. By correlating these data with the clinical state of the patient from which each population is isolated and the eventual clinical outcome, we hope to understand why TAA-specific T cells are protective in some patients but not in others. Lastly, we will dissect the factors which mediate T cell dysfunction in cancer by testing various individual and combinations of immunomodulatory agents to induce or reverse T cell dysfunction (Aim 4). Together, these data should lead to a better understanding of the biology of the T cell response to melanoma, and may lead to improvements in current cancer immunotherapy approaches.