bioRxivImmunologyPreprint
A Pan-Cancer Census of Dominant Tumor Immune Archetypes
A. J. Combes, B. Samad, J. Tsui, N. W. Chew, P. Yan, G. C. Reeder, D. Kushnoor, A. Shen, B. Davidson, A. J. Barczac, M. Adkisson, A. Edwards, M. Naser, K. C. Barry, T. Courau, T. Hammoudi, R. J. Arguello, A. A. Rao, A. B. Olshen, Immunoprofiler Consortium, C. Cai, J. Zhan, K. C. Davis, R. K. Kelley, J. S. Chapman, , M. F. Krummel
Abstract
Cancers display significant heterogeneity with respect to tissue of origin, driver mutations and other features of the surrounding tissue. It is likely that persistent tumors differentially engage inherent patterns-here Archetypes-of the immune system, to both benefit from a tumor immune microenvironment (TIME) and to disengage tumor-targeting. To discover dominant immune system archetypes, the Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub compartments uncovered archetypes that exist across indications. These Immune composition-based archetypes differentiate tumors based upon unique immune and tumor gene-expression patterns. Archetypes discovered this way also tie closely to well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune infiltration and provides a rational path forward to learn how to modulate these patterns to improve therapy. O_FIG O_LINKSMALLFIG WIDTH=182 HEIGHT=200 SRC="FIGDIR/small/441344v1_ufig1.gif" ALT="Figure 1"> View larger version (77K): org.highwire.dtl.DTLVardef@55a5ccorg.highwire.dtl.DTLVardef@f8205corg.highwire.dtl.DTLVardef@1480b8org.highwire.dtl.DTLVardef@eb94e_HPS_FORMAT_FIGEXP M_FIG C_FIG
- organism: human
- assay: flow cytometry
- assay: bulk RNA-seq
- research focus: cell type annotation
- research focus: clustering
- approach: statistical model
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