Computational Immunogenomics Group

Our group focuses on advancing insights into the genomic basis of tumorigenesis and its interplay with the immune system. We perform large-scale tumor genomic analyses matched with a comprehensive profiling of the tumor immune microenvironment to better understand the tumor-immune crosstalk. Our final goal is to leverage this knowledge to improve the clinical development of tailored immunotherapies.

Cancer is characterized by an uncontrolled growth of cells that are not cleared by the immune system. Every tumor has a unique composition of genomic alterations acquired over the evolution of the tumorigenic clone. While tumors often harbor hundreds to thousands of genomic alterations, only a handful are responsible for the tumorigenic process (so-called drivers). Driver alterations tend to be cancer-type specific (Martínez-Jiménez et al. 2020) and are generally conserved between primary and metastatic lesions (Martínez-Jiménez et al. 2023).

It is however becoming increasingly clear that tumor genomic alterations are not the only promoters of tumor development and metastasis. Other factors including cancer immune escape also play a critical role. In this context, we are interested in developing computational models to 1) further understand the interplay between tumor evolution and the immune system, and 2) harness this knowledge to improve the clinical development of tailored immunotherapies.

Our approach is based on integrating the genomic portrait of tumors (based on whole-exome/genome sequencing), which includes the identification of simple and complex tumor specific alterations, rationalized prioritization of tumor neoantigens, and characterization of tumor HLA-I status and other immune escape alterations; combined with a quantitative portrayal of the tumor immune microenvironment (using bulk transcriptomics/proteomics immune deconvolution, single cell and geospatial immune profiling, and TCR-sequencing). As an example, we have recently performed a large-scale analysis of the prevalence and impact of genetic immune escape alterations across >6,000 primary and metastatic tumors (Martinez-Jiménez, Priestley et al. 2023).

Thanks to our close collaboration with the Hartwig Medical Foundation we have access to one of the largest resources of whole genome sequenced tumors and full tumor transcriptomes (currently >7,000 patients, https://database.hartwigmedicalfoundation.nl/). Moreover, in-house data is generated to support the validation of our analyses and address specific questions that require more targeted analysis.

Since our VHIO group was established in February 2023, we have obtained competitive funding to support multiple projects, participated in several national and international conferences, and we published five peer-reviewed papers in top journals.