Project 3: Tools for Capturing Immune Cell/Cancer Cell Interactions in Cancer Immunotherapies and Combination Immunotherapies

项目3：在癌症免疫治疗中捕获免疫细胞/癌细胞相互作用的工具， 联合免疫疗法。 摘要： 癌症免疫疗法是2013年的科学突破[1]，具有巨大的前景， 围绕两个免疫治疗类的兴奋。第1类由免疫检查点抑制剂组成[2， 3]，如程序性死亡（PD）-1/L1阻断。这些药物会增加癌症的易感性 免疫系统的攻击。PD-1/L1阻断在多种癌症中的临床试验，但由以下工作领导： 黑色素瘤[4]已经证明了癌症治疗的新时代[5，6]。第2类治疗是连续性细胞转移 （ACT）[7，8]，其寻求增强抗肿瘤免疫系统功能。技术支持这些 癌症免疫治疗一直是NSBCC的主题[9-13]，我们的免疫监测工具用于 几个试验和病人研究。最近的免疫治疗成功提高了患者的期望。我们 提出技术来推进科学，将这一承诺带给更多的患者。我们会审问 肿瘤模型和癌症患者对单一和联合治疗有反应或产生耐药性 免疫疗法，对所有接受免疫疗法的癌症患者具有预期的影响。我们专注于 在体内和体外测量癌细胞和肿瘤浸润淋巴细胞之间的相互作用 （TILs）。这种相互作用可以杀死肿瘤细胞，但也可以促进肿瘤细胞的活化。 抵抗这种杀戮。这一主题对于改善ACT和检查点抑制剂疗法至关重要。

PROJECT 3: Tools for Capturing Immune Cell/Cancer Cell Interactions in Cancer Immunotherapies and Combination Immunotherapies. ABSTRACT: Cancer Immunotherapy was Science Breakthrough of the Year 2013[1], with tremendous promise and excitement surrounding two immunotherapy classes. Class 1 is comprised of immune checkpoint inhibitors[2, 3], such as for Programmed Death (PD)-1/L1 blockade. These drugs can increase the susceptibility of cancer cells to immune system attack. The clinical testing of PD-1/L1 blockade in multiple cancers, but led by work in melanoma[4], has demonstrated a new era in cancer treatment[5, 6]. Therapy Class 2 is Adoptive Cell Transfer (ACT)[7, 8], which seeks to strengthen the anti-tumor immune system function. Technologies to support these cancer immunotherapies have been an NSBCC theme [9-13], and our immune monitoring tools are used in several trials and patient studies. Recent immunotherapy successes have raised patient expectations. We propose technologies to advance the science to bring this promise to more patients. We will interrogate how tumor models and patients with cancer respond or become resistant to single and combination immunotherapies, with anticipated implications for all cancer patients receiving immunotherapies. We focus on measuring, in vivo and in vitro, the interactions between the cancer cells and tumor infiltrating lymphocytes (TILs). Such interactions can yield tumor cell killing, but can also promote the activation of tumor cell resistance to such killing. This theme is central for improving both ACT and checkpoint inhibitor therapies.