ENDOGENOUS T CELL RESPONSES TO MELANOMA

描述（申请人描述）： 内源性免疫系统在控制癌症中的确切作用 发展仍不明朗。 肿瘤细胞通常被认为是 非免疫原性的，因为它们是“自身”来源的。 然而，肿瘤反应性 淋巴细胞可以从患有多种癌症的患者中分离。 是 目前还不清楚这些淋巴细胞起什么作用，为什么它们不能保护 主持人 使用鼠B细胞白血病/淋巴瘤（BCL 1）模型， 研究人员已经表明，早期强有力的抗肿瘤T细胞应答 即使在肿瘤易感宿主中也会发生（1）。 然而，这件事的性质 非保护性反应不同于保护性反应 在MHC匹配的抗肿瘤宿主中。 易感和耐药宿主 发展对BCL 1的极化T细胞应答，其与临床 结果（1）. 因此，抗肿瘤免疫应答的性质似乎 这对于其后续发展和最终临床结果至关重要。 BCL 1构成了一个多功能的模型来研究为什么内源性免疫 在某些情况下，免疫反应成功地控制了肿瘤的发展，但却失败了。 在其他人身上。 在这一建议中，调查人员将采取多方面的 了解肿瘤识别的分子基础的方法， 免疫调节机制决定了每个反应。 他们有 开发了一种识别抗原特异性T细胞的新方法 肽/MHC四聚体，并将使这些试剂追踪 BCL 1反应性T细胞在每个反应中的发育命运。 最后， 他们将讨论肿瘤细胞如何随着内源性免疫系统的改变而改变， 以及他们如何积极参与塑造这一 反应 这些知识不仅可以揭示重要的生物学 过程，但可能有助于使癌症免疫疗法更接近现实。

DESCRIPTION (Applicant's Description): The precise role of the endogenous immune system in controlling cancer development remains unclear. Tumor cells are generally thought to be non-immunogenic since they are of "self" origin. However, tumor-reactive lymphocytes can be isolated from patients with many types of cancer. It is unclear what role these lymphocytes play and why they fail to protect the host. Using a murine B cell leukemia/lymphoma (BCL1) model, the investigators have shown that a vigorous early anti-tumor T cell response develops even in a tumor-susceptible host (1). However, the nature of this non-protective response is different from the protective response produced in a MHC-matched tumor-resistant host. Susceptible and resistant hosts develop polarized T cell responses to BCL1 which correlate with clinical outcome (1). Thus, the nature of the anti-tumor immune response seems critical to its subsequent development and the eventual clinical outcome. BCL1 constitutes a versatile model to study why the endogenous immune response succeeds in controlling tumor development in some cases, but fails in others. In this proposal, the investigators will take a multi-faceted approach to understand the molecular basis of tumor recognition and the immune regulatory mechanisms which determine each response. They have developed a novel method of identifying antigen-specific T cells using peptide/MHC tetramers and will make these reagents to trace the developmental fates of BCL1-reactive T cells in each response. Finally, they will address how the tumor cells may change as the endogenous immune response develops and how they may actively participate in shaping this response. This knowledge will not only shed light on important biological processes, but may help bring cancer immunotherapy closer to reality.