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We report here strategic functionalization of the Wnt5a mimetic peptide ligand Foxy5 on a polydimethylsiloxane elastomer substrate to enhance the mechanotransduction and activation of cytotoxic CD8+ T cells by triggering the noncanonical Wnt signaling. This new mechanoregulatory ligand platform can be widely applied in the fundamental research of mechano-immunology and further the development of novel immunotherapies.

Graphical abstract: Surface presentation of the noncanonical Wnt5a motif to cytotoxic CD8+ T-cells promotes their mechanotransduction and activation

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