Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity.

JSON

Garre E, Rhost S, Gustafsson A, Szeponik L, Araujo TF, Quiding-Järbrink M, Helou K, Ståhlberg A, Landberg G

Commun Biol 8 (1) 621 [2025-04-16; online 2025-04-16]

Recent advances as well as obstacles for immune-based cancer treatment strategies, highlight the notable impact of patient cancer microenvironments on the immune cells and immune targets. Here, we use patient-derived scaffolds (PDS) generated from 110 primary breast cancers to monitor the impact of the cancer microenvironment on immune regulators. Pronounced variation in PD-L1 expression is observed in cancer cells adapted to different patient scaffolds. This variation is further linked to clinical observations and correlated with specific proteins detected in the cell-free PDSs using mass spectrometry. When adding T cells to the PDS-based cancer cultures, the killing efficiency of activated T cells vary between the cultures, whereas non-activated T cells modulate the cancer cell PD-L1 expression to treatment-predictive values, matching killing capacities of activated T cells. Surviving cancer cells show enrichment in cancer stem cell and epithelial-to-mesenchymal transition (EMT) features, suggesting that T cells may not efficiently target cells with metastatic potential. We conclude that clinically relevant insights in how to optimally target and guide immune-based cancer therapies can be obtained by including patient-derived scaffolds and cues from the cancer microenvironment in cancer patient handling and drug development.

Glycoproteomics and MS Proteomics [Service]

PubMed 40240529

DOI 10.1038/s42003-025-08054-3

Crossref 10.1038/s42003-025-08054-3

pmc: PMC12003762
pii: 10.1038/s42003-025-08054-3