核心 2：免疫表型核心-猫眼课题宝

核心 2：免疫表型核心

批准号：

9906884

负责人：

ROBERT H PIERCE

金额：

$34.38万

依托单位：

UNIVERSITY OF WASHINGTON

依托单位国家：

美国

项目类别：

财政年份：

资助国家：

美国

项目状态：

未结题

起止时间：

至

来源：

https://reporter.nih.gov/project-details/9906884

关键词：

Address Adoptive Transfer Affinity Antibodies Antigen Presentation Pathway Area Biological Assay Biostatistics Core CD8-Positive T-Lymphocytes Cell Communication Cell Density Cell Line Cells Characteristics Collaborations Color Complex Data Disease Down-Regulation Elements Future Generations Genetic Transcription Glean Goals Histopathology Hybridomas Immune Immune Evasion Immune response Immunization Immunobiology Immunohistochemistry Immunooncology Immunophenotyping Immunotherapy In Situ Hybridization Intervention Lead Learning Merkel cell carcinoma Methods Microscopic Mining Mus Operative Surgical Procedures Oryctolagus cuniculus PD-1 blockade Patients Phenotype Preparation RNA Radiation Rattus Recurrence Research Sampling Series Services Slide Social Network Specimen Statistical Data Interpretation Stromal Cells T-Lymphocyte Technology Testing Tissue Microarray Tissues Transgenic Organisms Translating Tumor Immunity Tumor Tissue Tumor-infiltrating immune cells Validation Viral Virus Xenograft Model Xenograft procedure anti-PD-1 anti-PD-L1 antibodies anti-PD1 antibodies anti-tumor immune response antitumor effect base checkpoint therapy clinical development density design human monoclonal antibodies immune resistance immunogenic immunopathology immunoregulation improved innovation insight laser capture microdissection melanoma nanobodies neoplastic cell oncology trial prevent programmed cell death ligand 1 programmed cell death protein 1 programs response screening seropositive tool tumor tumor microenvironment tumor-immune system interactions ultraviolet damage

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中文摘要

翻译

翻译后摘要：免疫表型核心这项研究计划的一个中心统一假设是，MCC -病毒和紫外线损伤相关 - 是一种高度免疫原性的肿瘤，因此可以进行免疫肿瘤学干预。这许多患者体内存在病毒特异性T细胞和抗体也支持了这一假设在接受抗PD-1或抗PD-L1单药治疗的转移性MCC患者中，ORR约为50% 单克隆抗体（mAb）。不幸的是，许多患者仍然对PD-1阻断没有反应。的免疫表型核心的首要目标是提供尖端的，基于幻灯片的技术，询问肿瘤微环境，特别是应用多参数免疫组织化学（mIHC）了解肿瘤微环境（TME）中发生的关键细胞-细胞相互作用，使有效的抗肿瘤免疫应答成为可能或失效。我们预计，这些机械的见解将为未来MCC患者的联合免疫肿瘤学试验提供信息。

英文摘要

Abstract: Immunophenotyping Core A central unifying hypothesis of this research program is that MCC – both viral and UV-damage associated - is a highly immunogenic tumor and, consequently, amenable to immune-oncologic intervention. This hypothesis is supported by the presence of virus-specific T cells and antibodies in many of the patients as well as an approximate 50% ORR in metastatic MCC patients treated with monotherapy anti-PD-1 or anti-PD-L1 monoclonal antibodies (mAbs). Unfortunately, many patients still fail to respond to PD-1 blockade. The overarching goal of the Immunophenotyping Core is to provide cutting-edge, slide-based technologies to interrogate the tumor microenvironment, in particular, to apply multiparametric immunohistochemistry (mIHC) to understanding the critical cell-cell interactions occurring within the tumor microenvironment (TME) that either enable or disable productive anti-tumor immune responses. We anticipate that these mechanistic insights will inform future combination immune-oncology trials in MCC patients.

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