Zlatko Trajanoski

Abstract Summary: We have developed ClueGO, an easy to use Cytoscape plug-in that strongly improves biological interpretation of large lists of genes. ClueGO integrates Gene Ontology (GO) terms as well as KEGG/BioCarta pathways and creates a functionally organized GO/pathway term network. It can analyze one or compare two lists of genes and comprehensively visualizes functionally grouped terms. A one-click update option allows ClueGO to automatically download the most recent GO/KEGG release at any time. ClueGO provides an intuitive representation of the analysis results and can be optionally used in conjunction with the GOlorize plug-in. Availability: http://www.ici.upmc.fr/cluego/cluegoDownload.shtml Contact: jerome.galon@crc.jussieu.fr Supplementary information: Supplementary data are available at Bioinformatics online.

The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunological data (the type, density, and location of immune cells within the tumor samples) were found to be a better predictor of patient survival than the histopathological methods currently used to stage colorectal cancer. The results were validated in two additional patient populations. These data support the hypothesis that the adaptive immune response influences the behavior of human tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.

The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia.at/). Cellular characterization of the immune infiltrates showed that tumor genotypes determine immunophenotypes and tumor escape mechanisms. Using machine learning, we identified determinants of tumor immunogenicity and developed a scoring scheme for the quantification termed immunophenoscore. The immunophenoscore was a superior predictor of response to anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death protein 1 (anti-PD-1) antibodies in two independent validation cohorts. Our findings and this resource may help inform cancer immunotherapy and facilitate the development of precision immuno-oncology.

The role of tumor-infiltrating immune cells in the early metastatic invasion of colorectal cancer is unknown.