Cancer immunotherapies have emerged as highly promising approaches to treat cancer patients, particularly since they can be applied across different tissue and cancer types, although clinical efficacy has been limited to a subset of cancer patients. Translational studies with strong focus on biomarkers are critical to understanding the tumor-immune interface. Although numerous technologies for tumor and immune profiling are applied to NCI sponsored immunotherapy trials, standardization of both assay protocols and data analysis methods is crucial to data integration and comparisons across studies for biomarker identification. This underlines the need for data harmonization and creation of uniform analysis pipelines. We propose to establish the Cancer Immunology Data Commons (CIDC) at the Dana-Farber Cancer Institute with the goal of advancing translational research efforts using biomarkers to aid in the further development of cancer immunotherapy. The short-term objectives of this application are to establish and manage the data repository for biomarkers and associated clinical data for Cancer Immune Monitoring and Analysis Centers (CIMACs), and provide an informatics environment for integrative multi- dimensional analysis across different studies and storage of data generated. Specifically, we propose to:
Aim 1, coordinate with the CIMAC and Laboratory Coordinating Committee (LCC) to harmonize establish assay protocols and data format standards;
Aim 2, develop a centralized data repository and management system, and coordinate CIMAC data submission to the CIDC;
Aim 3, develop uniform bioinformatics processing pipelines and computing infrastructure for computationally intensive analyses for the CIMACs and the larger research community;
Aim 4, provide bioinformatics algorithms to enable integrative and correlative analysis of CIMAC data and integrate other accessible databases and resources for biomarker discovery;
Aim 5, develop centralized role-based data access functions with advanced programming interface to enable sharing of CIMAC data;
Aim 6, develop interactive web visualization functions to enable investigators and the immunology communities to examine the CIMAC data;
and Aim 7, coordinate within the CIMACs-CIDC Network logistic and scientific activities for biomarker discovery and validation. At the conclusion, we will have established a biomarker repository for all data and results generated by CIMACs, supplemented with standardized informatics tools for integration with other accessible databases, and compatible for data contribution and secondary analyses by external researchers. These efforts will provide bioinformatics support for the CIMACs-CIDC Network. The established Data Commons will also provide the foundation for a future immuno-oncology data resource for the larger research community.
Establishing biomarkers of drug response and resistance is of utmost importance to cancer immunotherapy in order to improve overall efficacy, minimize side effects, and reduce costs. The current network of NCI- supported clinical trials lacks standardization in data acquisition and processing, and require significant data integration and bioinformatics efforts. Our work will build the infrastructure for a centralized biomarker data repository and state-of-the-art informatics tools.
|Pan, Deng; Kobayashi, Aya; Jiang, Peng et al. (2018) A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science 359:770-775|
|Miao, Diana; Margolis, Claire A; Gao, Wenhua et al. (2018) Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 359:801-806|
|Cader, Fathima Zumla; Schackmann, Ron C J; Hu, Xihao et al. (2018) Mass cytometry of Hodgkin lymphoma reveals a CD4+ regulatory T-cell-rich and exhausted T-effector microenvironment. Blood 132:825-836|