Abstract
Cancer Hallmarks have been indispensable to rationalize the complex phenotypic properties acquired by cancer cells and their surrounding tumor microenvironment (TME) as they progress from normalcy to malignancy. While great insights have been gained from their use to understand bulk tissue transcriptomics, our knowledge remained incomplete, as it was not possible to determine the origin and relative localization of the activity of each Cancer Hallmark within tumor tissues. Thanks to recent advances in spatial transcriptomics, we can now explore the spatial contribution of each compartment within a tumor to each Cancer Hallmark at near single-cell resolution. Here, we used spatial transcriptomics from fifteen different primary tumor samples from seven tissues to quantify the contribution of the main tumor compartments -cancer cells and the TME- to each of thirteen Cancer Hallmarks. Our results revealed a Pan-Cancer architecture: with the activity of some hallmarks consistently coming from the cancer compartment across all cancer types (Cancer-associated hallmarks) and the activity of others consistently coming from the TME (TME-associated hallmarks). Furthermore, we observed that even within each compartment (cancer or TME) there was a consistent internal architecture, as many of these hallmarks exhibited higher activity at the border between compartments. Our study provides the first spatial map of Cancer Hallmark activities in tumors at almost cellular resolution, paving the way for a better understanding of the underpinnings of hallmark acquisition by tumor cell types.
Competing Interest Statement
E.P-P is part of the Clinical Translational Research Network sponsored by 10x Genomics
