What is it about?

Current anticancer strategies largely disregard the immune-suppressive tumor matrix and are poised to have limited outcomes. We describe the MAtrix REgulating MOtif (MAREMO) peptide, an agent with a broad spectrum of actions that reactivates the body’s immune defense against cancer. This peptide targets tenascin-C, a highly prominent and tumor-promoting component of the tumor matrix, and blocks tenascin-C signaling, thereby triggering antitumor immunity and inhibiting tumor cell expansion and phenotypic plasticity. The MAREMO peptide also subdues the tumor bed by depleting fibroblasts and restoring the function of the few remaining blood vessels, ideally suited for improving immune checkpoint therapy. Thus, targeting tenascin-C with the MAREMO peptide represents a powerful anticancer strategy with a broad spectrum of inhibition against multiple cancer-promoting actions.

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Why is it important?

The tumor extracellular matrix forming dense impenetrable barriers blocks the infiltration of immune cells into the tumor. Moreover, the tumor matrix retains immune cells so that they cannot fight the tumor. The described MAREMO peptide is abolishing these matrix barriers and thus allows immune cells to enter the tumor to fight the cancer.

Perspectives

In some promising therapies that reactivate the body`s own immune defence such as immune checkpoint or chimeric antigen receptor (CAR)-T cell therapy the impenetrable and immune suppressive matrix is an obstacle. It needs to be seen whether the MAREMO peptide can improve these anti-cancer treatment strategies.

Gertraud Orend
University Strasbourg

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This page is a summary of: Targeting the MAtrix REgulating MOtif abolishes several hallmarks of cancer, triggering antitumor immunity, Proceedings of the National Academy of Sciences, October 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2404485121.
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