Emerging evidence revealed important roles of tumor neoantigens in generating spontaneous antitumor immune responses and predicting clinical responses to immunotherapies 1 , 2 . Despite the presence of numerous neoantigens, complete tumor elimination rarely occurs in many patients, due to failures in mounting a sufficient and lasting antitumor immune response 3 , 4 . Here, we show that durable neoantigen-specific immunity is regulated by messenger RNA (mRNA) N 6 -methyadenosine (m 6 A) methylation through the m 6 A-binding protein YTHDF1 5 . In contrast to wild-type mice, Ythdf1 -deficient ( Ythdf1 −/− ) mice exhibit an elevated antigen-specific CD8 + T cell antitumor response. Loss of YTHDF1 in classical dendritic cells (cDCs) enhanced the cross-presentation of tumor antigen and the cross-priming of CD8 + T cells in vivo . Mechanistically, transcripts encoding lysosomal proteases are marked by m 6 A and recognized by YTHDF1. Binding of YTHDF1 to these transcripts elevates translation of lysosomal cathepsins in DCs, with the inhibition of cathepsins markedly enhancing cross-presentation of the wild-type DCs. Furthermore, the therapeutic efficacy of PD-L1 checkpoint blockade is enhanced in Ythdf1 −/− mice, implicating YTHDF1 as a new potential therapeutic target in anticancer immunotherapy.

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Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory-based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be “normal” after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge.