Tumour evolution and microenvironment interactions in 2D and 3D space
This Learning Wednesday paper note highlights “Tumour evolution and microenvironment interactions in 2D and 3D space.” The study is relevant to tumour evolution and microenvironment interactions across 2D and 3D space, with a focus on how three-dimensional tissue context can change what researchers see and measure.
Selected notes from the paper
“To study the spatial interactions among cancer and non-cancer cells, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST).”
“To describe tumour structures and habitats, we defined ‘tumour microregions’ as spatially distinct cancer cell clusters separated by stromal components.”
“We further grouped microregions with shared genetic alterations into ‘spatial subclones’.”
“We identified increased metabolic activity at the centre and increased antigen presentation along the leading edges of microregions.”
“We reconstructed 3D tumour structures by co-registering 48 serial ST sections from 16 samples, which provided insights into the spatial organization and heterogeneity of tumours.”
“We identified both immune hot and cold neighbourhoods and enhanced immune exhaustion markers surrounding the 3D subclones.”
“We demonstrate that there are distinct genetic clones within these microregions with specific copy number variations (CNVs) and with differential activity within oncogenic pathways, particularly the MYC pathway.”
“These reconstructions highlight tumour–immune interphase niches and interactions.”
“Primary tumours generally had more small microregions (66.3%) compared to metastases (40.2%), which had more medium-sized microregions (43.2%).”
“Larger microregions were predominantly found in metastases (16.3% compared with 3.2% in primary).”
“We identified multiple spatial subclones in sections from 4 cancer types: BRCA (17 sections), PDAC (10 sections), CRC (6 sections) and RCC (2 sections).”
“Although histology indicated a fibrotic separation between the two subclones, multiple shared clonal CNVs suggested a common origin.”
“Primary PDAC samples, despite their smaller microregions, also contained multiple spatial subclones.”
“We observed greater similarity within subclones compared with between different subclones.”
“We further investigated whether different transcriptional programs exist in tumour microregion centres (cores) compared to their leading edges.”
“Malignant cells in the core are actively undergoing protein translation, whereas those at the edges are involved in tumour migration and immune modulation.”
“3D reconstruction offers increased sensitivity for investigating heterogeneous tumour microenvironments.”
From an Alpenglow perspective, this paper is useful because it connects tumour evolution and microenvironment interactions across 2D and 3D space with a broader need in 3D spatial biology, measuring tissue architecture across depth while preserving context for quantitative analysis.
