Prognostic significance of spatial immune profiles in human solid cancers

Immune‐based tumor characteristics in the context of tumor heterogeneity are associated with suppression as well as promotion of cancer progression in various tumor types. As immunity typically functions based on intercellular contacts and short‐distance cytokine communications, the location and spatial relationships of the tumor immune microenvironment can provide a framework to understand the biology and potential predictive biomarkers related to disease outcomes. Immune spatial analysis is a newly emerging form of cancer research based on recent methodological advances in in situ single‐cell analysis, where cell‐cell interaction and the tissue architecture can be analyzed in relation to phenotyping the tumor immune heterogeneity. Spatial characteristics of tumors can be stratified into the tissue architecture level and the single‐cell level. At the tissue architecture level, the prognostic significance of the density of immune cell lineages, particularly T cells, is leveraged by understanding longitudinal changes in cell distribution in the tissue architecture such as intra‐tumoral and peri‐tumoral regions, and invasive margins. At the single‐cell level, the proximity of the tumor to the immune cells correlates with disease aggressiveness and therapeutic resistance, providing evidence to understand biological interactions and characteristics of the tumor immune microenvironment. In this review, we summarize recent findings regarding spatial information of the tumor immune microenvironment and review advances and challenges in spatial single‐cell analysis toward developing tissue‐based biomarkers rooted in the immune spatial landscape. The tumor immune microenvironment is characterized by multiple layers of spatial information. The whole tumor is dissected by tissue segments such as intratumoral and peritumoral regions at the tissue structure level, and by cell‐cell spatial relationships at the single‐cell level.