CORE--IMMUNOTHERAPY

免疫监测设施的建立是为了提供辅助免疫分析， 评估免疫疗法对免疫功能的影响的临床方案，认为免疫功能对消除肿瘤很重要。所提供的服务主要针对（1）鉴定通过免疫疗法改变的淋巴细胞群体和免疫功能，以及（2）估计癌症患者中T细胞受体库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重点是细胞毒性T淋巴细胞（CTL），因为它们具有溶解肿瘤细胞和分泌细胞因子的能力。最重要的两 肿瘤特异性CTL功能的测定包括通过（1）流式细胞术测定结合包括肿瘤相关肽的HLA I类二聚体/四聚体的CTL的频率和（2）使用Elispot测定来测定响应于肿瘤相关抗原/肽而分泌IFN γ或IL-5的CTL的频率来估计肿瘤特异性CTL的频率。通过基于RT-PCR的CD 4+和CD 8 + T细胞表达的α和β转录物的光谱分析来评估T细胞受体（TcR）库的多样性。包括TCR库的分析证实了 推动了这个设施的发展。从历史上看，监测设施一直专注于识别与免疫治疗相关的特定免疫功能的变化。我们认为，要理解这些治疗相关变化的重要性，需要评估癌症的免疫潜力 患者在治疗前。因此，了解患者的免疫应答与适当匹配的健康人的免疫应答之间的关系至关重要。此外，肿瘤特异性免疫应答必须与肿瘤对有效免疫应答的适应相关地进行评估，因为这两种动态力之间的相互作用通常包括确定临床结果的重要因素。因此，免疫监测设施在评估肿瘤特异性免疫应答中发挥着核心作用，将这些应答与患者相对于健康个体的免疫潜力相关联， 将肿瘤特异性反应与肿瘤免疫选择的相反力量联系起来。虽然该设施不直接参与评价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综合分析的策略。

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.