Stromal cells are tissue cells, primarily fibroblasts, and form the supporting tissue in which a tumor is located. There are various types of fibroblasts in the tumor with different functions: Some inhibit the immune system by forming connective tissue that shields the tumor cells from the immune system. Some promote metastasis and the formation of new blood vessels, thereby supplying oxygen and nutrients to the tumor. Still others promote resistance to therapy. On a particularly positive note, some fibroblasts promote the immune system in the fight against the tumor, e.g., antigen-presenting stromal cells. These are found in mini lymph nodes, known as tertiary lymphoid structures (TLS), and can present antigens from tumors and efficiently stimulate the immune system—especially T cells and B cells—in these mini lymph nodes.
Tumor neighborhood has thus far received insufficient attention
The progression of colorectal cancer is strongly influenced by this microenvironment, i.e., the “neighborhood” of the tumor. Until now, however, there has been little information on the spatial distribution of stromal cell subtypes in colorectal cancer and the clinical implications of this distribution.
The team identified eight different stromal cells located directly in the tumor or in its immediate vicinity. How their presence affects the prognosis of the disease depends on where they are located—on the surface or in mini lymph nodes near the tumor—and whether they organize themselves with the nerve growth factor receptor (NGFR) or occur in combination with certain enzymes or proteins. “The study provides a rationale for considering spatial stromal biomarkers in the prognosis of colorectal cancer. Furthermore, the presence of NGFR and stromal cells in mini lymph nodes could become a clinically applicable marker for personalized therapy,” says Dietmar Herndler-Brandstetter from the Center for Cancer Research at the Medical University of Vienna.
Spatial location and interaction decoded using computer technology
The researchers used computer-assisted analyses to examine the gene activity of individual cells (single-cell RNA sequencing). In addition, state-of-the-art multiplex imaging made seven different proteins visible simultaneously on a tissue sample. Artificial intelligence (HALO software) was used to evaluate the data and identify different cell types—such as cancer, immune, and connective tissue cells—and determine their exact location in the tumor. By combining these methods, it was possible to determine not only which cells are present in the tumor, but also how they interact spatially with each other.
The research was supported by the Austrian Science Fund (FWF), the Austrian Academy of Sciences, the City of Vienna, the Fellinger Cancer Research Foundation, a Georg Stumpf Cancer Research Scholarship, and the Vienna Science and Technology Fund (WWTF).
Publication: Cancer Letters
Spatial organization of stromal subtypes stratifies colorectal cancer patients and predicts clinical outcomes
Magdalena Frank, Giulia Ghirardello, James Malcolm Howie, Nina Braun, Rebecca Zirnbauer, Carmen Stecher, Stephan Gruener, Heinz Regele, Iros Barozzi, Michael Bergmann, Johannes Laengle*, Dietmar Herndler-Brandstetter*
DOI: 10.1016/j.canlet.2025.218228
https://www.sciencedirect.com/science/article/pii/S0304383525008006?via%3Dihub