Understanding the heterogeneity of the tumor microenvironment (TME) and its functional impact in solid tumors requires detailed examination of its cellular composition, the functional states of its cell populations, and their spatial organization within defined microenvironmental niches. This presentation will showcase data from an ongoing study utilizing the Harmonic Output of Stromal Traits (HOST), a research-driven framework for characterizing subsets of TME cells. HOST computes quantitative scores, called HOST-Factors, that distinguish pro-tumor and anti-tumor functional statuses across cellular populations and their respective niches. In particular, this talk will highlight the use of the HOST-Factor for profiling human pancreatic cancer-associated fibroblasts (CAFs) alongside key immunogenic and immunotolerant immune infiltrates, with a focus on evaluating their overall tumor-restrictive (TR) versus tumor-supportive (TS) roles. 

Pancreatic ductal adenocarcinoma (PDAC) is profoundly influenced by its CAF-rich TME, which consists of active fibroblasts forming functional units with their self-generated extracellular matrix. To assess how this TME responds to therapy using the fibroblastic HOST-Factor, we are analyzing surgical specimens collected from a clinical trial at Fox Chase Cancer Center. 

Our integrated workflow combines a curated set of CAF and immune cell biomarkers, automated high-plex immunofluorescence microscopy, and AI-guided image analysis using Visiopharm®. This pipeline assigns single-cell HOST-Factor values, enabling spatial mapping of functionally distinct CAFs and immune cells. By identifying TS and TR neighborhoods within the TME, this approach could offer novel insights into the fibroblastic and immune landscape’s response to therapy and open the possibility to support more precise patient stratification for personalized treatment decisions.

Janusz Franco-Barraza, MD, PhD

Janusz Franco-Barraza, MD, PhD is an Assistant Research Professor and Manager of the Spatial Immuno-Proteomics Facility at Fox Chase Cancer Center. His research is dedicated to uncovering how cancer-associated fibroblasts (CAFs) shape the tumor microenvironment and contribute to either tumor progression or restraint. Recognized for his expertise in high-plex immunofluorescence and AI-driven spatial analysis, Dr Franco-Barraza studies the dynamics of fibroblastic biology using relevant biomarker signatures that reveal the functional states of CAFs and their relationship to tumor development. His work provides insights that may help predict patient outcomes and responses to cancer therapies.