A Pan-Cancer Census of Dominant Tumor Immune Archetypes

Abstract

SUMMARYCancers 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.

Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer

“…Further comprehensive analysis of key myeloid populations revealed distinct network connections between different myeloid cell types and T cell subsets, including Tregs and effector T cells. This is consistent with an archetypal organization of immune systems in tumors -collections of cell types that move together as modules 51 -and improved classification of patients such that we could identify those with effective antitumor T cell responses.…”

“…Notably, recent work focused on ascertaining the different immune archetypes across solid tumors suggests that these patient groups span cancer type 51 .…”

Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer

“…Further comprehensive analysis of key myeloid populations revealed distinct network connections between different myeloid cell types and T cell subsets, including Tregs and effector T cells. This is consistent with an archetypal organization of immune systems in tumors -collections of cell types that move together as modules 51 -and improved classification of patients such that we could identify those with effective antitumor T cell responses. 6 associated genes (e.g.…”

Multi-Parameter Quantitative Imaging of Tumor Microenvironments Reveals Perivascular Immune Niches Associated With Anti-Tumor Immunity

“…Tumors are structurally complex tissues, made up of malignant cancer cells and non-malignant host cells, including stromal cells, blood and lymphatic endothelial cells, as well as diverse subsets of immune cells with pro and anti-inflammatory properties, which collectively shape the tumor microenvironment (TME) (27)(28)(29)(30). Advanced imaging approaches have demonstrated a high degree of diversity for both cellular composition and spatial organization of cells across different tumor types, among individuals and even within individual tissues, indicating marked heterogeneity and complexity of the TME (3,16,(31)(32)(33)(34).…”