Cancer cells make unique form of collagen, protecting them from immune response

In its normal form, collagen is a heterotrimer consisting of two α1 chains and one α2 chain, which assemble to form a triple-helix structure as part of the extracellular matrix. However, when studying human pancreatic cancer cell lines, the researchers discovered the cells expressed only the α1 gene (COL1a1), whereas fibroblasts expressed both genes.

Further analysis revealed that cancer cells have silenced the α2 gene (COL1a2) through epigenetic hypermethylation, resulting in a cancer-specific collagen 'homotrimer' made up of three α1 chains.

To investigate the real-world effects of this observation, the researchers created knockout mouse models of pancreatic cancer with COL1a1 deleted only in cancer cells. Loss of this cancer-specific homotrimer reduced cancer cell proliferation and reprogrammed the tumor microbiome. This led to lower immunosuppression, which was associated with increased T cell infiltration and elimination of cancer cells.

Additionally, these knockout mice responded more favorably to anti-PD1 immunotherapy, suggesting that targeting this cancer-specific collagen could help boost the anti-tumor immune response.

Researchers said no other cell in the normal human body makes this unique collagen, so it offers tremendous potential for the development of highly specific therapies that may improve patient responses to treatment. On many levels, this is a fundamental discovery and a prime example of how basic science unravels important findings that could later benefit our patients.

Reference: "Cancer cells make unique form of collagen, protecting them from immune response"; Cancer Cell.