CORE--IMMUNOTHERAPY

建立免疫监测设施是为了在以下方面提供辅助免疫学分析 评估免疫疗法对被认为对消除肿瘤重要的免疫功能的影响的临床方案。所提供的服务主要针对(1)确定通过免疫疗法改变的淋巴细胞群体和免疫功能，以及(2)评估癌症患者T细胞受体谱系的多样性以及治疗方式对T细胞受体多样性的影响。肿瘤特异性免疫反应的分析主要集中在细胞毒性T淋巴细胞(CTL)上，因为CTL具有溶解肿瘤细胞和分泌细胞因子的能力。两个最重要的 肿瘤特异性CTL功能的检测包括通过以下方法估计肿瘤特异性CTL的频率：(1)结合包含肿瘤相关多肽的HLAI类二聚体/四聚体的CTL频率的估计；(2)使用ELISPOT试验估计分泌IFNGamma或IL-5的CTL对肿瘤相关抗原/多肽的反应频率。T细胞受体(TCR)谱系的多样性是通过基于RT-PCR的由CD4+和CD8+T细胞表达的α和β转录本的谱型来评估的。对TCR曲目的分析体现了这样一种哲学 推动了这个设施的发展。从历史上看，监测设施的重点是识别与免疫治疗相关的特定免疫功能的变化。我们认为，了解这些与治疗相关的变化的重要性需要评估癌症的免疫潜力。 患者在治疗前。因此，了解患者的免疫反应与适当匹配的健康人的免疫反应之间的关系是至关重要的。此外，必须根据肿瘤对有效免疫反应的适应性来评估肿瘤特异性免疫反应，因为这两种动力之间的相互作用预期包括决定临床结果的重要因素。因此，免疫监测设备在评估肿瘤特异性免疫反应方面发挥着核心作用，将这些反应与患者相对于健康人的免疫潜力联系起来，以及 将肿瘤特异性反应与肿瘤免疫选择的相反力量联系起来。虽然该机构没有直接参与评估肿瘤特异性免疫的所有这些方面，即免疫选择，但它密切参与制定这种全面分析的战略。

The Immune Monitoring Facility was established to provide ancillary, immunological analyses in clinical protocols to evaluate the effects of immunotherapy on immunological functions that are believed to be important for the elimination of tumors. The offered services are principally directed toward (1) identifying lymphocyte populations and immunological functions that are altered by immunotherapy and (2) estimating the diversity of T cell receptor repertoires in cancer patients and the effects of treatment modalities on T cell receptor diversity. The analysis of tumor-specific immune responses focuses on cytotoxic T lymphocytes (CTL) due to their demonstrated abilities to lyse tumor cells and secrete cytokines. The two most important assays of tumor-specific CTL function involve the estimation of the frequencies of tumor-specific CTLs through (1) flow cytometric estimation of the frequencies of CTLs that bind HLA class I dimers/tetramers that include tumor-associated peptides and (2) the use of Elispot assays to estimate the frequencies of CTLs that secrete IFNgamma,or IL-5 in response to tumor-associated antigens/peptides. The diversity of T cell receptor (TcR) repertoire is evaluated through RT-PCR-based spectratyping of alpha and beta transcripts expressed by CD4 + and CD8 + T cells. The inclusion of analyses of TCR repertoire exemplifies the philosophy that has driven the evolution of this facility. Historically, monitoring facilities have focused on identifying shifts in specific immune functions that are related to immunotherapy. We have taken the view that understanding the importance of these therapy-related changes requires an evaluation of the immune potentials of cancer patients prior to treatment. Accordingly, it is essential to understand the relationship between immunological responses of patients and those of appropriately matched, healthy humans. Further, tumor-specific immune responses must be evaluated in relation to the adaptation of tumors to effective immune responses since the interplay between these two dynamic forces expectedly comprises an important factor in determining clinical outcome. Therefore, the Immune Monitoring Facility plays a central role in evaluating tumor-specific immune responses, relating these responses to the immune potentials of patients relative to healthy individuals, and relating tumor-specific responses to the opposing forces of tumor immunoselection. Although this Facility is not directly involved in evaluating all of these aspects of tumor-specific immunity, i.e. immunoselection, it is intimately involved in developing the strategy for such comprehensive analyses.