Document text
Principal Investigator: Heng Li
Organization: DANA-FARBER CANCER INST
Fiscal Year: 2020
Award: $423,633
Funding agency: National Cancer Institute
PROJECT SUMMARY
The repertoires of tumor-infiltrating T cells and B cells are rich sources of information about cancer-immune
interactions and provide insights on cancer immunotherapy targets. Efforts have been made to characterize B/T
cell repertoires in solid tumors using cell sorting followed by targeted deep sequencing. However, these
approaches may produce biased estimates during tissue disaggregation and can be expensive when applied to
large sample cohorts. Massively parallel mRNA sequencing (RNA-seq) technology has become the mainstream
method to profile gene expression and thousands of solid tumor RNA-seq profiles are available in the public
domain. The rich collection of tumor RNA-seq datasets provides an alternative approach to study tumor-infiltrating
B/T cell repertoires in solid tumors. Our team has recently developed a statistical method TIMER for deconvolving
different immune components in the tumor microenvironment, and TRUST for inferring the hypervariable
complementarity determining regions (CDRs) of the tumor infiltrating T cell receptor (TCR) repertoire from bulk
tumor RNA-seq data in the public domain.
Our preliminary analysis indicated that there are approximately ten times as many B cell receptor (BCR) reads
and TCR reads, suggesting that extracting the BCR repertoires from bulk tumor RNA-seq could reveal important
insights on B cell mediated tumor immunity. The aims of this proposal are: to extend our TRUST algorithm to
extract B cell receptor (BCR) repertoires from tumor RNA-seq data, and identify somatic hypermutations and
immunoglobin class switches (Aim 1); to systematically analyze TCR and BCR repertoires from large scale tumor
RNA-seq cohorts, and develop a user friendly web interface to allow cancer immunologists or immuno-oncologists
to investigate tumor-immune associations (Aim 2); to promote the utility of our tumor immune resource through
collaborations, cloud sharing, and outreach (Aim 3).
We will deliver a robust bioinformatics algorithm to systematically identify BCR / TCR repertoires from bulk tumor
RNA-seq data and a user-friendly resource for cancer immunologists or immuno-oncologists to explore tumor-
immune interactions from large tumor profiling cohorts in the public as well as their unpublished data. The
successful execution of this proposal has the potential to inform clinical practice of cancer immunotherapies,
including adoptive T cell transfer, therapeutic cancer vaccines or antibodies. Our proposed cancer immunology
algorithm and resource will be a unique addition to the array of bioinformatics tools developed by the Information
Technology for Cancer Research at the National Cancer Institute.
Terms: <Algorithms><Antibodies><Antigens><Antineoplastic Vaccine><B blood cells><B cell><B cell receptor><B cell repertoire><B cells><B-Cells><B-Lymphocytes><B-cell><Bio-Informatics><Bioinformatics><Biological><Body Tissues><Cancer Treatment><Cancer Vaccines><Cancers><Cell Isolation><Cell Maturation><Cell Segregation><Cell Separation><Cell Separation Technology><Class Switching><Class Switchings><Clinic><Collaborations><Collection><Complementarity Determining Regions><Complimentarity Determining Region><Computational algorithm><Consumption><Data><Data Set><Dataset><Education and Outreach><Educational Mainstreaming><Gene Expression><Genomic Data Commons><Hypervariable Loop><Hypervariable Regions><Ig Somatic Hypermutation><Ig Variable Region><Immune><Immune infiltrates><Immune mediated therapy><Immune system><Immunes><Immunity><Immunoglobulin Class Switching><Immunoglobulin Class Switchings><Immunoglobulin Hypervariable Region><Immunoglobulin Somatic Hypermutation><Immunoglobulin V><Immunoglobulin V(D)J Rearrangement><Immunoglobulin Variable Region><Immunologically Directed Therapy><Immunologist><Immunotherapy><Infiltration><Informatics><Information Technology><Instruction and Outreach><Isotype Switching><Isotype Switchings><MHC Receptor><Mainstreaming><Major Histocompatibility Complex Receptor><Malignant Cell><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Mediating><Mediation><Methods><NCI Organization><National Cancer Institute><Negotiating><Negotiation><Neoplasm Vaccines><Oncologist><Patients><Property><Public Domains><RNA Seq><RNA analysis><RNA sequencing><RNAseq><Receptor Cell><Receptors, Antigen, B-Cell><Receptors, Antigen, T-Cell><Research Resources><Resources><Sampling><Solid Neoplasm><Solid Tumor><Source><Statistical Methods><T cell based therapeutics><T cell based therapy><T cell infiltration><T cell targeted therapeutics><T cell therapy><T cell tumor trafficking><T-Cell Receptor><T-Cells><T-Lymphocyte><T-Stage><T-cell receptor repertoire><TCGA><TCR repertoire><Technology><The Cancer Genome Atlas><Therapeutic><Time><Tissues><Training and Outreach><Tumor Immunity><Tumor Tissue><Tumor Vaccines><Tumor stage><Tumor-Infiltrating Lymphocytes><Tumor-infiltrating immune cells><Tutoring and Outreach><V(D)J Rearrangement><V(D)J Recombination><VDJ rearrangement><VDJ recombination><Variable Region><achievement Mainstream Education><adoptive T cell transfer><adoptive T-cell therapy><algorithm development><allergic/immunologic body system><allergic/immunologic organ system><anti-cancer immunotherapy><anti-cancer research><anti-cancer therapy><anti-tumor immunity><anticancer immunotherapy><anticancer research><anticancer therapy><antitumor immunity><bio-informatics infrastructure><bio-informatics resource><bio-informatics tool><bioinformatics infrastructure><bioinformatics resource><bioinformatics tool><cancer cell><cancer immunity><cancer immunology><cancer immunotherapy><cancer microenvironment><cancer research><cancer resource><cancer therapy><cancer type><cell sorting><clinical practice><cohort><computational resources><computer algorithm><computing resources><data mining><datamining><deep sequencing><genomic data><genomic data-set><genomic dataset><heuristics><immune cell infiltrate><immune infiltration><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based cancer therapies><immune-based therapies><immune-based treatments><immuno therapy><immunogen><immunoglobulin receptor><immunological diversity><immunotherapy for cancer><immunotherapy of cancer><improved><improved functioning><insight><internet resource><intratumoral immune cell><mRNA sequencing><mRNA-seq><malignancy><neoplasm immunology><neoplasm resource><neoplasm/cancer><novel><on-line compendium><on-line resource><online compendium><online resource><outreach><simulation><somatic hypermutation><sound><therapeutic T-cell platform><thymus derived lymphocyte><transcriptome sequencing><tumor><tumor immune cell><tumor immunology><tumor microenvironment><user-friendly><vaccine for cancer><web interface><web resource><web-based resource>