Research Background
Study Overview
A recent study published in PNAS, titled “Acquired resistance to immunotherapy by physical barriers with cancer cell–expressing collagens in non–small cell lung cancer,” investigates a previously underappreciated mechanism of immunotherapy resistance in non-small cell lung cancer (NSCLC).
Study Design
An Integrated Multi-Omics Strategy
To investigate the underlying resistance mechanisms, the research team integrated single-cell RNA sequencing, spatial transcriptomics, and proteomics, enabling molecular and spatial characterization of the tumor microenvironment from complementary perspectives.
Among these approaches, spatial transcriptomics provided important in situ evidence by preserving the spatial context of gene expression within tumor tissues. This information complemented single-cell RNA sequencing, which offers high-resolution cellular profiling but does not retain the original spatial positions of individual cells.
Research Highlights
Key Findings
Cancer Cells Contribute to a Dual-Layer Collagen Barrier
The study reports that cancer cells can secrete collagens that contribute to the formation of a dual-layer physical barrier within the tumor microenvironment.
Physical Barriers Restrict T-Cell Access and Tumor Cell Killing
This collagen-rich structure restricts T-cell infiltration and limits effective tumor cell killing, thereby contributing to acquired resistance to immunotherapy.
Research Significance
Implications for Immunotherapy Resistance Research
The findings highlight tumor cell-derived extracellular matrix components as active contributors to acquired immunotherapy resistance, showing how the physical organization of the tumor microenvironment can influence immune-cell access and antitumor activity.
The study also demonstrates the value of integrating single-cell and spatially resolved approaches. Together, these technologies connect detailed cellular profiles with the original tissue architecture, enabling a more complete view of resistance mechanisms within the tumor microenvironment.
BMKGENE Contribution
Supporting Spatial Characterization of the Tumor Microenvironment
BMKGENE is pleased to have supported this study by providing BMKMANU S1000 spatial transcriptomics sequencing services.
BMKMANU S1000 · Spatial Transcriptomics Sequencing
Original Publication
Wang, M., Wang, Y., Pan, X., et al. Acquired resistance to immunotherapy by physical barriers with cancer cell–expressing collagens in non–small cell lung cancer. Proceedings of the National Academy of Sciences 122(24), e2500019122 (2025). DOI: 10.1073/pnas.2500019122.
Post time: Sep-18-2026
