Targeting Erbin-mitochondria axis in platelets/ megakaryocytes promotes B cell-mediated antitumor immunity

The roles of platelets/megakaryocytes (MKs), the key components in the blood system,in the tumor microenvironment and antitumor immunity are unclear. In patients withcolorectal cancer, the number of platelets was significantly increased in patientswith metastasis, and Erbin expression was highly expressed in platelets from patientswith metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasisin mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient plateletshave increasing mitochondrial oxidative phosphorylation and secrete lipid metaboliteslike acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM.Notably, Acar enhanced the activity of mitochondrial electron transport chain complexand mitochondrial oxidative phosphorylation in B cells by acetylation of H3K27 epigenetically.Targeting Erbin in platelets/MKs by a nanovesicle system dramatically attenuated lungmetastasis in mice in vivo. Our study identifies an Erbin-mitochondria axis in platelets/MKs, which suppressesB cell-mediated antitumor immunity, suggesting a new way for the treatment of metastasis.