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 with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient platelets have increasing mitochondrial oxidative phosphorylation and secrete lipid metabolites like acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM. Notably, Acar enhanced the activity of mitochondrial electron transport chain complex and mitochondrial oxidative phosphorylation in B cells by acetylation of H3K27 epigenetically. Targeting Erbin in platelets/MKs by a nanovesicle system dramatically attenuated lung metastasis in mice in vivo. Our study identifies an Erbin-mitochondria axis in platelets/MKs, which suppresses B cell-mediated antitumor immunity, suggesting a new way for the treatment of metastasis. [Display omitted] • Erbin is key for functions of platelets/megakaryocytes in cancer progression • Platelets/megakaryocytes and B cells axis are crucial for niches of tumor immunity • Erbin-mitochondria axis is critical for antitumor immunity • Acyl-carnitine mediates mitochondrial function transfer between platelets and B cells Platelets/megakaryocytes are functionally associated with hemostasis and thrombosis. Zhang et al. found that Erbin deficiency platelets/megakaryocytes prefer to adhere B cells to mediate antitumor immunity, which was triggered by Erbin-mitochondria axis and platelets/megakaryocytes derived lipid metabolites. [ABSTRACT FROM AUTHOR]