Stromal fibroblast density

Cancer associated fibroblasts (CAFs) are activated fibroblasts found in the tumor stroma — the connective tissue surrounding cancer cells. Unlike normal quiescent fibroblasts, CAFs are reprogrammed by tumor-derived signals to support cancer growth through multiple mechanisms: extracellular matrix (ECM) remodeling, secretion of growth factors, immune modulation, and promotion of angiogenesis.

CAFs are central players in the desmoplastic reaction — the dense fibrotic stroma that characterizes many solid tumors, particularly pancreatic, breast, and colorectal cancers. They deposit and cross-link collagen, creating a stiff extracellular matrix that can physically exclude immune cells from the tumor (immune exclusion) and impede drug delivery. CAFs also secrete cytokines like TGF-β and IL-6 that promote epithelial-to-mesenchymal transition (EMT) and tumor cell invasion.

HistoAtlas measures stromal fibroblast density as the number of fibroblasts per mm² of stromal area:

$$\text{Density} = \frac{N_{\text{fibro}}^{\text{S}}}{A(\Omega_{\text{Stroma}})}$$

This cell-level quantification from H&E captures stromal cellularity in an interpretable, continuous metric across all 33 TCGA cancer types.

Fibroblast density captures overall stromal cellularity, but the spatial distribution of fibroblasts also matters. HistoAtlas measures peritumoral fibroblast enrichment (whether fibroblasts concentrate near the tumor boundary) and fibroblast-lymphocyte proximity (spatial relationship between fibroblasts and immune cells). Together, these features characterize the stromal compartment across cancers.