The role of tenascin-C in cancers



Gertraud Orend, a director of research at the Inserm and her team at the Immuno-rhumatologie moléculaire laboratory (Inserm U1109/University of Strasbourg), have demonstrated that the tenascin-C* molecule immobilises cytotoxic T lymphocytes, thus preventing them from reaching tumour cells in order to kill them. The results were published in the journal EMBO Molecular Medicine.

Tumour cells are embedded in a tumorous microenvironment composed of an extracellular matrix that defines the 3D configuration of the tissue. This extracellular matrix can also interact with the cells and regulate their behaviour. In this study, Gertraud Orend’s team demonstrated that one of these molecules in the extracellular matrix (tenascin-C) prevents the infiltration of cytotoxic T lymphocytes into the tumour and thus blocks the functions of these cells.

Based on these results, the team suggests that the release of cytotoxic tumour-infiltrating leukocytes (TILs) combined with “immune checkpoint therapy”** could enhance the reactivation of cytotoxic TILs and thus increase the effectiveness of the anti-tumour immune response.

Encouraged by these initial findings, the team is working on developing drugs to block the identified mechanism. In this way, the cytotoxic lymphocytes could be released from the extracellular matrix and enter the tumour to eliminate the tumour cells. If the results are conclusive, clinical trials could soon follow as some drugs targeting the “Matrix Release and Activation” of cytotoxic TILs identified by Gertraud Orend have already been approved by the FDA.

These results offer hope for improved diagnosis and cancer therapy, in particular for breast cancer.

*Tenascin-C is known to be overexpressed in breast cancer and to promote tumour progression.

**Immunotherapy used in the treatment of certain cancers

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