Discovering dominant tumor immune archetypes in a pan-cancer census.

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system—here "archetypes"—creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) 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 dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy. [Display omitted] • UCSF Immunoprofiler Initiative is a set of human tumors with multimodal linked data • Clustering upon 10 features identifies 12 unique tumor archetypes spanning cancer types • Each archetype concentrates similarities in additional immune and tumor features • Dominant archetypes aid in tumor classification and identifying therapeutic targets Tumors can be extremely heterogenous across multiple parameters. By identifying and classifying recurrent immune features across 12 different tumor types, a framework is provided toward understanding tumor immunity as well as identifying broad and common therapeutic targets. [ABSTRACT FROM AUTHOR]