Journal club review: Multiplex 3D Atlas
A tour de force paper by Lin et al from the Sorger Lab at Harvard. This paper is chock full of 3D tumor architecture, tertiary lymphoid structures and spatial heterogeneity in human colorectal cancer samples. Read our key findings from the paper below.
Lin et al. “Multiplex 3D atlas…in colorectal cancer” Cell, 2023.
Here are a few key findings from the paper:
Tertiary lymphoid structures (TLS) networks in 3D. One of the most surprising findings of this study is that many TLS are interconnected, complex, 3D networks of immune cells that can’t be fully visualized and may be missed using conventional 2D spatial biology methods. These networks have regional variation in cell types and polarization in relation to the tumor/stromal interface. The implications of this finding are vast for immunotherapy. How often do tumors have TLS displaying these networked properties? How does 3D TLS structure and cell type polarization influence immunotherapy efficacy?
Spatial Heterogeneity. TMA cores don’t cut it. In a whole-slide image from one sample, the true percentage of cytokeratin+ abundance cells was 45%, while TMAs from the same sample had cytokeratin+ cell abundance vary from 5% to 95%. The WSI contained 100x more cells than the TMAs, so variation is expected, but that is a lot of variation. We also see large amounts of variation in cell counts when sampling 100x more tissue with 3D imaging compared to 2D whole-slide images. This reinforces something we’ve seen in our research experience - when you only sample part of the tissue, you only get part of the answer..
3D tumor architecture. Tumor budding is not what it seems in 2D. Traditional 2D pathology defines tumor buds as no more than 4 tumor cells surrounded by stroma, located at the invasive front of the tumor. Lin et al. show that these “buds” are often thin, finger-like invasions connected to the main tumor mass. This finding has implications for diagnosis (Should the tumor bud criteria be revisited?) and biology (How often are tumor buds actually buds? Do finger-like protrusions and true buds have different molecular characteristics and aggressiveness?). We are excited to see more applications of 3D imaging like this which upend the traditional 2D interpretation of hidden structural information in tissue.
This summary only scratches the surface of the interesting work by Lin et al. Read the paper and let us know what you think at info@alpenglowbiosciences.com!