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REAKTHROUGHS IN BASIC BIO-medical sciences, including human genomics, stem cell biology, biomedical engineering, molecular biology, and immunology, over the past 5 decades have provided an unprecedented supply of information for improving human health. This revolutionary progress in basic science would not have happened without the public's long-term investment in and steadfast commitment to basic biomedical research. Translating the information gained through these basic discoveries into knowledge that will affect clinical practice and, ultimately, human health requires clinical research involving human subjects and human populations, as well as devel-opment of improved health services based on that research. This next scientific frontier deserves a correspond-

Low doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed. The clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells.

BackgroundTumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types.ResultsWe compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8+ T/Treg ratio are associated with improved survival, whereas Th2 cells and Tregs are associated with negative outcomes. Investigation of the association of immune infiltration patterns with the subclonal architecture of tumors shows that both APM and T cell levels are negatively associated with subclone number.ConclusionsOur analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1092-z) contains supplementary material, which is available to authorized users.