July 12, 2022

Probing the tumor microenvironment

Vanderbilt researchers used single-cell sequencing, imaging, and computational approaches to characterize the colonic tumor microenvironment, providing important insights to the components that play roles in colorectal tumor pathogenesis.

The tumor microenvironment, which includes epithelial, immune and connective tissue cells, plays important roles in the pathogenesis of colorectal tumors. 

Few studies have examined how the microenvironment changes as colorectal tumors transition from advanced adenomas to pre-invasive carcinomas. Ken Lau, PhD, and colleagues have now used single-cell RNA-sequencing, multiplex immunofluorescence imaging, and computational approaches to explore the colonic tumor microenvironment in mouse models of advanced adenoma (APC) and pre-invasive inflammation-induced cancer (AOM/DSS). 

The researchers found that colonic tumors in the APC and AOM/DSS models have distinct microenvironments. The AOM/DSS model microenvironment contains more diverse and abundant cancer-associated fibroblasts that spatially associate with neoplastic cells. Lau and colleagues also identified a unique squamous cell population, which increased following the cessation of chemotherapy, in the AOM/DSS model but not in the APC model. 

The findings, reported in Frontiers in Oncology, provide important insight into microenvironment components and their interactions in models that differ in the stage of colorectal tumor progression.

Paige Vega, a graduate student in Lau’s group, is the study’s first author. Other authors include Avlant Nilsson, PhD, Manu Kumar, Hiroaki Niitsu, MD, PhD, Alan Simmons, James Ro, Jiawei Wang, Zhengyi Chen, Brian Joughin, PhD, Wei Li, Eliot McKinley, PhD, Qi Liu, PhD, Joseph Roland, PhD, M. Kay Washington, MD, PhD, Robert Coffey, MD, and co-corresponding author Douglas Lauffenburger, PhD, from Massachusetts Institute of Technology. 

The research was supported by the National Institutes of Health (grants CA215798, DK103831, DK127687, CA197570, CA236733, HD007502, CA068485), Swedish Research Council and Nicholas Tierney GI Cancer Memorial Fund.