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The CSBC Research Center for Cancer Systems Immunology at MSKCC

MSKCC CSBC 癌症系统免疫学研究中心

基本信息

批准号：
9980798
负责人：
Christina S Leslie
金额：
$ 231.25万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-26 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9980798
关键词：
Address Adopted Algorithms Antibodies Area Biological Cancer Biology Cancer Center Cancer Model Cell Communication Cell Proliferation Cells Clinical Computer Analysis Computing Methodologies Data Development Disease Disease Progression Ecosystem Education and Outreach Educational workshop Epigenetic Process Goals Hematologic Neoplasms Heterogeneity Human Immune Immune Evasion Immune system Immunology Immunotherapeutic agent Immunotherapy In Vitro Innate Immune System Intervention Investigation Malignant Neoplasms Memorial Sloan-Kettering Cancer Center Methods Modeling Molecular Molecular Analysis Mus Mutation NCI Center for Cancer Research Natural Killer Cells Neoplasm Metastasis Patients Population Property Research Residual Tumors Resource Sharing Role Sampling Scientific Advances and Accomplishments Scientist Stromal Cells System Systems Biology T cell differentiation T cell therapy T-Lymphocyte Techniques Technology Testing Training Training Activity Training Programs Tumor Antigens Tumor-Infiltrating Lymphocytes cancer cell cancer immunotherapeutics cancer immunotherapy cancer initiation cancer therapy cancer type cell type design droplet sequencing epigenomics graduate student immune checkpoint blockade immunotherapy trials in silico in vivo innovation lectures live cell imaging machine learning method melanoma method development neoplastic cell novel outreach program patient response patient subsets programs response single cell analysis single-cell RNA sequencing statistical and machine learning symposium technology development tool transcriptome sequencing tumor tumor immunology tumor-immune system interactions tumorigenesis undergraduate student

项目摘要

SUMMARY Exciting clinical breakthroughs with checkpoint blockade antibodies and adoptive T cell transfers have transformed the field of cancer immunotherapy, demonstrating the power of harnessing the immune system to eliminate cancer cells. However, fundamental challenges and questions remain. Significant clinical responses have only been observed in a subset of patients and cancer types, and it is currently not known what biological properties of tumors determine clinical responses, nor what strategies to adopt in clinical contexts where current immunotherapies are ineffective. To ultimately address these clinical challenges and to design predictably effective cancer treatments, we must deepen our fundamental understanding of interactions between tumors and the immune system at the molecular, cellular, and systems levels. The CSBC Research Center for Cancer Systems Immunology at MSKCC will bring the tools of systems biology to investigate cancer-immune system interactions at multiple stages of disease progression to answer central questions in cancer immunology and inform the design of novel immunotherapeutic interventions. We have organized our Research Center around three central scientific projects that examine cancer-immune interactions at distinct stages of disease progression: cancer initiation and early tumorigenesis (Project I); established and progressing tumors (Project II); latent disease and metastasis in (Project III). In Project I, we will combine new epigenomics technologies and innovative single-cell analyses with state-of-the-art systems biology approaches to decipher the underlying molecular and epigenetic programs of dysfunctional tumor- specific T cell differentiation in early tumorigenesis. We will further elucidate how dynamics in the mutational tumor antigen landscape and stromal and immune cell populations determine such states and model and test in mouse and human tumors how distinct T cell states determine sensitivity to immune checkpoint blockade. In Project II, we will use quantitative analysis of cell types and cell states by functional, flow cytometric, population RNA-seq and droplet RNA sequencing together with ecological models of cancer, immune, and stromal cell populations to study the response of the tumor ecosystem to immunotherapeutic perturbations in established tumors. In Project III, we will examine the evolutionary dynamics of innate immune system control of metastatic disease, a new area of investigation in cancer immunology. We will investigate the heterogeneity of latent cancer cells in their capacity for immune evasion, and we will use quantitative methods, including live cell imaging, to model latent tumor cell evasion of innate immune control and the dynamics of cycles of latent cell proliferation and potential editing by NK cells. A Shared Resource Core will provide state-of-the-art single-cell droplet sequencing technology and computational analysis of single-cell RNA-seq data (scRNA- seq). This Shared Resource Core will be tasked with droplet sequencing technology development and design of novel algorithmic approaches and will interact with all three scientific Projects. Our Research Center will also carry out an innovative program of outreach and training activities at the local, national, and global levels to disseminate research findings in cancer systems immunology and to train young scientists in this emerging field.

总结