A pan-cancer landscape of interactions between solid tumors and infiltrating immune cell populations
By
David Tamborero,
Carlota Rubio-Perez,
Ferran Muinos,
Radhakrishnan Sabarinathan,
Josep M Piulats,
Aura Muntasell,
Rodrigo Dienstmann,
Nuria Lopez-Bigas,
Abel Gonzalez-Perez
Posted 21 Sep 2017
bioRxiv DOI: 10.1101/192286
(published DOI: 10.1158/1078-0432.ccr-17-3509)
Throughout their development, tumors are challenged by the immune system and acquire features to evade its surveillance. A systematic view of these traits is still lacking. Here, we identify genomic and transcriptomic traits associated to the immune-phenotype of 9,403 tumors of 29 solid cancers. In highly cytotoxic immune-phenotypes we found tumors with low clonal heterogeneity enriched by alterations of genes involved in epigenetic regulation, ubiquitin mediated proteolysis, antigen-presentation and cell-cell communication, which may drive resistance. Tumors with immune-phenotypes with mid cytotoxicity present an over-activation of processes involved in invasion and remodeling of neighboring tissues that may foster the recruitment of immune-suppressive cells. Tumors with poor cytotoxic immune-phenotype tend to be of more advanced stages and present frequent alterations in cell cycle, hedgehog, beta-catenin and TGF-beta pathways, which may drive the immune depletion. These results may be exploited to develop novel combinatorial targeting strategies involving immunotherapies.
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