Cancer-Immu is an open-access resource for exploring associations between onco-immunological genomic data and immunophenotype and thus reveals some important biological conclusions with implications for ICB-based immunotherapy. The Cancer-Immu currently contains 4,035 samples with both ICB response outcome and genomic profiling by either bulk sequencing or single-cell technologies. Each genomic profiling provides multiple types of features, including the known or novel signatures predictive of immunotherapy response. Genetic level is comprised of mutation, mutational loads/burden and mutational signature. Transcriptomic level includes expression, expression sum, expression relation pairs and immune cell components. Single-cell level provides gene/protein expression and specific cell population. Cancer-Immu provides meta-analysis and pan-cancer analysis modules for signature prioritization and specific signature assessment. Meta-analysis reveals consistent signatures across multiple study cohorts, while pan-cancer analysis enhances our ability to detect and analyze rare features by aggregating events across cohorts/tumor types.
News!
05-10-2024, Single-cell tumor immune atlases:
--ABTC atlas, Single-cell atlas of diverse immune populations in the advanced biliary tract cancer microenvironment.
--HCC atlas, A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma.
--STAD atlas, Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric Cancer.
--TICA atlas, A single-cell tumor immune atlas for precision oncology.
--Pan-T atlas, Pan-cancer single-cell landscape of tumor-infiltrating T cells.
--Pan-blueprint atlas, Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance.
download: R object of ABTC atlas
download: R object of HCC atlas
download: R object of STAD atlas
download: R object of TICA atlas
download: R object of pan-T atlas
download: R object of pan-blueprint atlas
08-22-2023, New added data:
--73 samples from 1 study, Pan-cancer analysis of advanced patient tumors reveals interactions between therapy and genomic landscapes.
08-18-2023, New added data:
--218 samples from 1 study, Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer.
07-20-2022, New added data:
--28 samples from 1 study, A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients.
06-19-2021, New added data:
--144 samples from 1 study, Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma.
03-07-2021, New added data:
--31 samples from 1 study, PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.
02-02-2021, New added data:
--348 samples from 1 study, TGFb attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.
--29 samples from 1 study, Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.
11-06-2020, New added data:
--15 samples from 1 study, Clonal replacement of tumor-specific T cells following PD-1 blockade.
10-25-2020, New added data:
--112 samples from 1 study, A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade.
@Vanderbilt University Medical Center
Center for Quantitative Sciences
497A Preston Research Building | Nashville, TN 37232 | 615-322-6618
PLEASE NOTE, due to different experimental designs and data processing methods, and additional covariates, some bias might be introduced in the aggregated dataset.
PLEASE NOTE, due to different experimental designs and data processing methods, and additional covariates, some bias might be introduced in the aggregated dataset.
PLEASE NOTE, due to different experimental designs and data processing methods, and additional covariates, some bias might be introduced in the aggregated dataset.
PLEASE NOTE, due to different experimental designs and data processing methods, and additional covariates, some bias might be introduced in the aggregated dataset.
PLEASE NOTE, due to different experimental designs and data processing methods, and additional covariates, some bias might be introduced in the aggregated dataset.
Example file for clinical data: Example_clinical_data.txt
The clinical data should contain 12 columns which are 'Disease','PatientID','data_source','treatment type','treatment status','PFS.status','RECIST','OS.status','OS','PFS','Age' and 'Gender'.
Disease
: required. Cancer type.
PatientID
: required. A unique identifier for each sample.
data_source
: required. A character string specifying the experiment name (e.g. 'experiment_1', 'MyExperiment', 'User', etc).
treatment type
: required. A character string specifying the treatment type, for example, 'anti-PD-1', 'anti-CTLA-4', 'anti-IL17RA', etc.
treatment status
: required. Flaglist string specifying pre-treatment or on-treatment. Please insert one of 'Pre', 'On', or 'Unknown' for each sample.
PFS.status
: required. Flaglist string specifying the therapeutic outcome. Please insert one of 'response', 'nonresponse' or 'Unknown' for each sample.
RECIST
: optional. RECIST is a standard way to measure how well a cancer patient responds to treatment, please refer to NIH. Please specify one of 'CR', 'PR', 'PD', 'SD' or 'NA'.
OS.status
: optional. Specifying one of 'living', 'deceased' or 'NA'.
OS
: optional. A number specifying overall survival days. If no data available fill in NA.
PFS
: optional. A number specifying progression free survival days. If no data available fill in NA.
Age
: optional.
Gender
: optional. Specifying one of 'Male', 'Female' or 'NA'.
Please keep your column names same with above columns' names. If no data available please fill in NA.
Example file for transcriptome data: Example_transcriptome_data.txt
The transcriptome data where each row represents a sample and each column represents a gene. And the gene expression values should be normalized and log2 transfered.
PLEASE NOTE: the 'PatientID' of each sample should match to the 'PatientID' column of clinical data.
Example file for mutation data: Example_mutation_data.txt
The mutation data should contain 7 columns which are 'PatientID','gene','variant_class', 'Chromosome', 'pos', 'ref' and 'alt'.
PatientID
: required. Sample identifier. NOTE: the 'PatientID' column of mutation data should match to the 'PatientID' column of clinical data.
gene
: required. Gene symbols
variant_class
: required. Flaglist string specifying variant type. For example, 'Missense_Mutation', 'Nonsense_Mutation', 'Silent', 'Intron', and etc.
Chromosome
: required. Flaglist string or number specifying chromosome. For example, both of 'chr1','chr2' and '1', '2' are acceptable.
pos
: required. Mutation position. Default is set to the UCSC hg19 assembly, which corresponds to the GRCh37 assembly.
ref
: required. reference base.
alt
: required. alternate base.
Please keep your column names same with above columns' names. If no data available please fill in NA.
Example file for gene-cell data: Example_gene_cell_data.txt
The gene-cell data where each row represents a cell and each column represents a gene. And the gene expression values should be read counts.
Example file for patient-cell data: Example_patient_cell_data.txt
The patient-cell data should contain 2 columns which are 'PatientID' and 'cells'.
PatientID
: required. Sample identifier. NOTE: the 'PatientID' column of mutation data should match to the 'PatientID' column of clinical data.
cells
: required. Cell names
Please keep your column names same with above columns' names. If no data available please fill in NA.
PLEASE NOTE: the 'PatientID' of each sample should match to the 'PatientID' column of clinical data. the 'cells' should match to the column names of gene-cell data.
This may take a while
Cancer-Immu explores the associations of multi-angle features with immunotherapy response, which are derived from a variety types of genomic data, including genetic, transcriptomic and single cell. Genetic level is comprised of mutation, mutational loads/burden, and mutational signature. Transcriptomic level includes expression, expression sum, expression relation pairs and immune cell components. Single-cell level contains gene/protein expression and specific cell population (Figure 1).
Figure 1. Data content of Cancer-Immu.
Cancer-Immu provides meta-analysis and pan-cancer analysis modules to detect consistent and rare omics features associated with immunotherapy response across multiple cohorts. Each analysis includes two functions, signature prioritization and specific signature assessment.
Signatures prioritization in the meta-analysis is aimed to rank signatures based on their common associations with immunotherapy response across multiple cohorts. The association test is performed in each individual cohort. Firstly, we scaled signature values in each individual cohort to z-scores with mean of zero and standard deviation of one. And then effect size and standard error of effect size were calculated from binomial logistic regression using z-scores as terms and immune checkpoint inhibitor therapy response as values. The meta-analysis results of the associations between signature and response (odds ratios) can be estimated by combining individual result in each study via meta-analysis by meta package in R. Then, as a final step, the signatures are ranked by the meta-analysis p-value/FDR (top panel of Figure 2). The detailed view of the association between one signature and ICB responsiveness, OS and PFS, is provided by specific signature assessment module (bottom panel of Figure 2).
Figure 2. Meta-analysis module.
Pan-cancer analysis evaluates and ranks signatures based on their associations with ICB-based response in the aggregated cohort. To detect the associations between rare events and ICB-based response in a large-scale dataset rather than in multiple individual datasets, we aggregated datasets as one big dataset. Some genetic data, including mutation, mutation signatures and immune cell components, were integrated directly without any further process since genomic features are generally comparable and have negligible batch effects across datasets. For incomparable data, to remove platform- or laboratory-specific batch effects, we performed batch correction by using removeBatchEffect function of limma R package along with a design matrix to preserve the response effect. Signatures prioritization calculates the associations between signatures and ICB-based response and then ranks signatures based on the p-value in the aggregated cohort. Specific signature assessment provides a detailed view of the associations between one given signature and ICB therapeutic response, OS and PFS in the aggregated cohort (Figure 3).
Figure 3. Pan-cancer analysis module.
If you have questions, comments, or find any bugs with Cancer-Immu, please contact
Dr. Qi Liu <
qi.liu@vumc.org
>
Dr. Jing Yang <
jing.yang@vumc.org
>
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Yang J, Liu Q, Shyr Y. A Large-Scale Meta-Analysis Reveals Positive Feedback between Macrophages and T Cells That Sensitizes Tumors to Immunotherapy. Cancer Res. 2024 Feb 15;84(4):626-638. doi: 10.1158/0008-5472.CAN-23-2006. PMID: 38117502; PMCID: PMC10867621.
@Vanderbilt University Medical Center
Center for Quantitative Sciences
497A Preston Research Building | Nashville, TN 37232 | 615-322-6618