Deciphering the tumor microenvironment using patient-derived scaffolds and single-cell triomics

The tumor microenvironment shapes how cancer cells grow, adapt, and respond to therapy. Yet most laboratory models, such as two-dimensional monolayer cultures, strip away the extracellular matrix and tissue architecture that define tumors in patients. Patient-derived scaffolds, decellularized tumor tissue that retains its native structure and composition, recreate in vivo-like growth conditions when repopulated with tumor cells of interest.

In this live webinar, Dr. Anders Ståhlberg will present how his group has applied patient-derived scaffolds in breast cancer, colon cancer, and sarcoma to study the cellular and non-cellular tumor microenvironment. Molecular characterization of scaffolds and repopulated cells revealed cell-to-cell signaling and biological processes that drive tumor development. Single-cell triomics on Mission Bio's Tapestri platform, using a targeted approach, then measured DNA, RNA, and protein within the same cells, linking genotype directly to phenotype.

In breast cancer cells grown in monolayers and in scaffolds, with and without chemotherapy, triomics reliably resolved distinct subpopulations across genetic, transcriptional, and protein biomarkers. Chemotherapy shifted these subpopulations and their biomarker expression, while scaffolds derived from different patients' tumors influenced cell heterogeneity and drug resistance in distinct ways, reflecting each tumor's unique microenvironment.

Together, this approach can help reveal how the tumor microenvironment shapes cellular heterogeneity, phenotypes, and treatment response, and provide new insight into the mechanisms underlying tumor development and therapy resistance.

Key takeaways

• Context changes the cell. The same breast cancer cells behave differently in patient-derived scaffolds than in monolayer culture, which shows why in vivo-like models matter for biology and drug testing.
• Every patient's microenvironment is different. Scaffolds from different breast tumors affected cell heterogeneity and drug resistance differently. The non-cellular microenvironment is an active driver, not a passive backdrop.
• One model across tumor types. The scaffold approach has been applied in breast cancer, colon cancer, and sarcoma, and gives a reusable framework for studying tumor–microenvironment interactions.
• Three analytes, one cell. Single-cell triomics on Tapestri measures DNA, RNA, and protein from the same cell, linking genotype directly to transcriptional and protein phenotype. Separate single-analyte assays can't make that link.
• Treatment response at clonal resolution. Chemotherapy shifted subpopulations and biomarker expression, so triomics can follow how tumor cells adapt under therapeutic pressure.
• Translational relevance. Combining patient-derived scaffolds with single-cell multi-omics gives a physiologically relevant platform for studying drug resistance and for patient-specific evaluation of therapy response.

Learning objectives

By the end of this webinar, attendees will be able to:

• Explain how patient-derived scaffolds, made from decellularized tumor tissue, recreate in vivo-like features when repopulated with tumor cells of interest
• Describe how scaffold models in breast cancer, colon cancer, and sarcoma reveal the roles of the cellular and non-cellular tumor microenvironment in tumor development
• Understand how molecular characterization of scaffolds and repopulated cells uncovers cell-to-cell signaling and biological processes
• Apply single-cell triomics to resolve tumor heterogeneity and cellular phenotypes

Who should attend

Cancer biologists, translational and pharma researchers in oncology drug discovery, and scientists working with 3D or microenvironment models who want single-cell, multi-omic resolution.