Periodic Reporting for period 5 - IMMUcan (Integrated IMMUnoprofiling of large adaptive CANcer patients cohorts)
Reporting period: 2023-03-01 to 2024-02-29
Immune checkpoint inhibitors have shown promising results in some cancer types, but biomarkers to select patients that might respond to the treatment still need to be established. Similarly, rationale for combining immune checkpoint inhibitors with conventional therapy, targeted agents, or other immune checkpoint inhibitors are lacking. Finally, a better understanding of resistance mechanisms (primary and secondary) to immune checkpoint inhibitors is still lacking. One of the main challenges is the limited amount of comprehensive empirical data that integrate molecular, cellular, and clinical information to guide future translational and clinical research development.
IMMUcan is proposing an inclusive and integrated European immuno-oncology profiling platform. IMMUcan will generate broad molecular and cellular profiling data of the tumour and its microenvironment from high-risk cancer patients. The molecular and cellular information will be integrated with clinical data, to better understand how the immune system and tumours interact, and the impact of current therapeutic interventions.
IMMUcan will access human biological material including tumour tissue, blood, stool, and saliva as well as longitudinal clinical information from up to 3000 patients treated with standard of care treatment, including immune checkpoints inhibitors, or enrolled in clinical trials. IMMUcan is focusing on colorectal, lung, head & neck, breast, and renal cancers. About half of the patients will be recruited via SPECTA, the integrated research infrastructure under EORTC legal sponsorship. The other half will come from independently planned and funded academic clinical trials or cohort studies.
A centralized workflow of samples, via a state-of-the-art biobank, will increase reproducibility, as all tissues will be processed and stored in a uniform way, following proofed SOPs. IMMUcan will perform in depth immune profiling with cutting edge technologies including the following:
- Spatial distribution of immune cell subtypes: imaging mass cytometry (Cytof) and multiplex immunofluorescence (IF);
- RNAseq analysis: Total RNA;
- DNA analysis: whole exome sequencing (WES);
- Single cell on immune populations based on 10x Genomics technology, including dendritic cell deep characterization;
- Liquid CyTOF on peripheral blood mononuclear cells (PBMCs);
- Circulating tumor DNA (ctDNA) and exosome analysis;
IMMUcan will develop a sustainable data platform and legal contractual framework where participants from both academia and industry can pursue their own independent investigations utilizing the IMMUcan data and effectively test and improve the functioning and relevance of the database throughout the duration of the project. IMMUcan will also support the future use of the data generated by the project by the research community.
Lay version of of this summary is available from https://immucan.eu/patients
IMMUcan is proposing an inclusive and integrated European immuno-oncology profiling platform. IMMUcan will generate broad molecular and cellular profiling data of the tumour and its microenvironment from high-risk cancer patients. The molecular and cellular information will be integrated with clinical data, to better understand how the immune system and tumours interact, and the impact of current therapeutic interventions.
IMMUcan will access human biological material including tumour tissue, blood, stool, and saliva as well as longitudinal clinical information from up to 3000 patients treated with standard of care treatment, including immune checkpoints inhibitors, or enrolled in clinical trials. IMMUcan is focusing on colorectal, lung, head & neck, breast, and renal cancers. About half of the patients will be recruited via SPECTA, the integrated research infrastructure under EORTC legal sponsorship. The other half will come from independently planned and funded academic clinical trials or cohort studies.
A centralized workflow of samples, via a state-of-the-art biobank, will increase reproducibility, as all tissues will be processed and stored in a uniform way, following proofed SOPs. IMMUcan will perform in depth immune profiling with cutting edge technologies including the following:
- Spatial distribution of immune cell subtypes: imaging mass cytometry (Cytof) and multiplex immunofluorescence (IF);
- RNAseq analysis: Total RNA;
- DNA analysis: whole exome sequencing (WES);
- Single cell on immune populations based on 10x Genomics technology, including dendritic cell deep characterization;
- Liquid CyTOF on peripheral blood mononuclear cells (PBMCs);
- Circulating tumor DNA (ctDNA) and exosome analysis;
IMMUcan will develop a sustainable data platform and legal contractual framework where participants from both academia and industry can pursue their own independent investigations utilizing the IMMUcan data and effectively test and improve the functioning and relevance of the database throughout the duration of the project. IMMUcan will also support the future use of the data generated by the project by the research community.
Lay version of of this summary is available from https://immucan.eu/patients
IMMUcan biological sample and data workflows are up and running for more than 4 years now. 1230 patients were confirmed eligible for IMMUcan as of Feb 2024. In order to accelerate the access to sample and data, the Consortium secured access to sample from five external trials (EORTC 1559 UPSTREAM, EORTC SPECTAlung, UZL Dutrelasco, IJB-Synergy, NVALT-30 Dedication) and four retrospective sample collections for the CRC indication (UZL, CLB and UCL) and the RCC indication with UroCCR. Current collaboration already contributed to additional 566 eligible patients at the end of Feb 2024 in addition to the SPECTA patients and should lead to more than 600 patients before the end of the IMMUcan project.
In the broad profiling, RNAseq analysis and WES of germline and tumor DNA are running smoothly, with more than 1,100 molecular reports generated by SIB in collaboration with EORTC and sent to treating physicians. 44 molecular tumour board meetings took place between EORTC and treating physicians to discuss treatment options taking based on IMMUcan results. Tools for selecting regions of interest for the Imaging Mass Cytometry based on immunofluorescence data have been newly developed by SIB, UZH and CHUV and are up and running. CHUV implemented and run on all samples a new software, in house deigned, for IF analysis, called IFQuant. The upload of imaging mass cytometry (IMC) data on the KMS is on-going. Complete broad profiling datasets (RNA-seq, WES, multiplex IF and IMC) are now available for 742 samples from 718 patients. Relatively complete datasets (e.g. only one of the four profiling modalities missing) have been generated from 1,535 samples from 1,402 patients.
On the deep profiling side, KUL completed the recruitment phase of the Dutrelasco trial. All the planned scRNA-seq and spatial transcriptomics activities have been performed. CyTOF analyses and exosome data generation were completed for all Dutrelasco samples. All 20 patients were included for scRNAseq in January 2023 and shallow and deep sequencing was finalized in June 2023. Data were uploaded on KMS in March 2024 . For CyTOF profiling on blood samples, KCL teams have finalized the alterations on the CyTOF panel, including re-titrations on the antibodies. CyTOF sampling analyses were finalized in March 2024, as well as exosome profiling. Data is under preparation for upload to the KMS.
IMMUcan Knowledge Management System (KMS) is live and active. The KMS is providing a centralized storage of clinical, molecular and cellular data collected or generated with IMMUcan. The KMS is providing samples and data tracking from the IBBL to the different labs, H&E slides viewer, platform for generating patient molecular report. A patient view summarizes major clinical, molecular, mIF and IMC data for a given patient. An instance of cBioPortal enables cohort clinical and molecular data mining. Several tools are integrated in the KMS, including a tool to explore results of scRNAseq experiments, IFQuant to analyse images from multiplex fluorenscence images, a tool to align images of consecutive tissue sections and a curation tool for drug names and lines of therapies. EORTC, CHUV and SIB are working on cleaning and formatting the clinical data, especially the detailed treatment history of each patient. The cohort datasets are accessible to the IMMUcan partners via the KMS after clearing the GDPR risk assessment.
In WP6, biomarker validation examples that were formulated in 2022 can now be tested on newly generated data from new patients. Concrete examples of how automatic biomarker calling can be performed with real-time interim evaluation on currently available patients will be shared through the IMMUcan file server.
WP7 was discussing with WP4.1 and 4.2 labs the integration of IF/IMC results with molecular data, Integration of deep and broad profiling data, Immune cell type-based deconvolution of whole tumor RNAseq. The single-cell directory was completed and single cell database is on the KMS covering 32 public datasets. The related publication will be submitted shortly to the consortium for review.
The project website targeting clinicians, study sponsors, researchers and the specific section targeting patients is live since last period and maintained with IMMUcan latest news and regular communications released in professional social media linked to the project.
In the broad profiling, RNAseq analysis and WES of germline and tumor DNA are running smoothly, with more than 1,100 molecular reports generated by SIB in collaboration with EORTC and sent to treating physicians. 44 molecular tumour board meetings took place between EORTC and treating physicians to discuss treatment options taking based on IMMUcan results. Tools for selecting regions of interest for the Imaging Mass Cytometry based on immunofluorescence data have been newly developed by SIB, UZH and CHUV and are up and running. CHUV implemented and run on all samples a new software, in house deigned, for IF analysis, called IFQuant. The upload of imaging mass cytometry (IMC) data on the KMS is on-going. Complete broad profiling datasets (RNA-seq, WES, multiplex IF and IMC) are now available for 742 samples from 718 patients. Relatively complete datasets (e.g. only one of the four profiling modalities missing) have been generated from 1,535 samples from 1,402 patients.
On the deep profiling side, KUL completed the recruitment phase of the Dutrelasco trial. All the planned scRNA-seq and spatial transcriptomics activities have been performed. CyTOF analyses and exosome data generation were completed for all Dutrelasco samples. All 20 patients were included for scRNAseq in January 2023 and shallow and deep sequencing was finalized in June 2023. Data were uploaded on KMS in March 2024 . For CyTOF profiling on blood samples, KCL teams have finalized the alterations on the CyTOF panel, including re-titrations on the antibodies. CyTOF sampling analyses were finalized in March 2024, as well as exosome profiling. Data is under preparation for upload to the KMS.
IMMUcan Knowledge Management System (KMS) is live and active. The KMS is providing a centralized storage of clinical, molecular and cellular data collected or generated with IMMUcan. The KMS is providing samples and data tracking from the IBBL to the different labs, H&E slides viewer, platform for generating patient molecular report. A patient view summarizes major clinical, molecular, mIF and IMC data for a given patient. An instance of cBioPortal enables cohort clinical and molecular data mining. Several tools are integrated in the KMS, including a tool to explore results of scRNAseq experiments, IFQuant to analyse images from multiplex fluorenscence images, a tool to align images of consecutive tissue sections and a curation tool for drug names and lines of therapies. EORTC, CHUV and SIB are working on cleaning and formatting the clinical data, especially the detailed treatment history of each patient. The cohort datasets are accessible to the IMMUcan partners via the KMS after clearing the GDPR risk assessment.
In WP6, biomarker validation examples that were formulated in 2022 can now be tested on newly generated data from new patients. Concrete examples of how automatic biomarker calling can be performed with real-time interim evaluation on currently available patients will be shared through the IMMUcan file server.
WP7 was discussing with WP4.1 and 4.2 labs the integration of IF/IMC results with molecular data, Integration of deep and broad profiling data, Immune cell type-based deconvolution of whole tumor RNAseq. The single-cell directory was completed and single cell database is on the KMS covering 32 public datasets. The related publication will be submitted shortly to the consortium for review.
The project website targeting clinicians, study sponsors, researchers and the specific section targeting patients is live since last period and maintained with IMMUcan latest news and regular communications released in professional social media linked to the project.