Abstract

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 the tumor immune microenvironment (TIME) and to disengage tumor-targeting. To discover dominant immune system archetypes across diverse cancer types, we processed in an unbiased way 364 individual tumors across 12 cancer indications using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained on cell sub compartments uncovered archetypes that exist across indications and are durable to increased granularity in higher dimensions. Immune composition-based archetypes differentiate tumors based upon the distribution of large unrelated collections of immune and tumor gene-expression patterns. Archetypes discovered this way also tie closely to well-established classifications of tumor biology. The resultant Immunoprofiler Initiative (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 study cancer immunity and learn how to modulate these patterns to improve therapy. Citation Format: Matthew F. Krummel. Spatiotemporal definitions of immune archetypes across cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY24-01.

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