Human CD1c+ DCs are critical cellular mediators of immune responses induced by immunogenic cell death

Chemotherapeutics, including the platinum compounds oxaliplatin (OXP) and cisplatin (CDDP), are standard care of treatment for cancer. Although chemotherapy has long been considered immunosuppressive, evidence now suggests that certain cytotoxic agents can efficiently stimulate antitumor responses, through the induction of a form of apoptosis, called immunogenic cell death (ICD). ICD is characterized by exposure of calreticulin and heat shock proteins (HSPs), secretion of ATP and release of high-mobility group box 1 (HMGB1). Proper activation of the immune system relies on the integration of these signals by dendritic cells (DCs). Studies on the crucial role of DCs, in the context of ICD, have been performed using mouse models or human in vitro-generated monocyte-derived DCs (moDCs), which do not fully recapitulate the in vivo situation. Here, we explore the effect of platinum-induced ICD on phenotype and function of human blood circulating DCs. Tumor cells were treated with OXP or CDDP and induction of ICD was investigated. We show that both platinum drugs triggered translocation of calreticulin and HSP70, as well as the release of ATP and HMGB1. Platinum treatment increased phagocytosis of tumor fragments by human blood DCs and enhanced phenotypic maturation of blood myeloid and plasmacytoid DCs. Moreover, upon interaction with platinum-treated tumor cells, CD1c+ DCs efficiently stimulated allogeneic proliferation of T lymphocytes. Together, our observations indicate that platinum-treated tumor cells may exert an active stimulatory effect on human blood DCs. In particular, these data suggest that CD1c+ DCs are critical mediators of immune responses induced by ICD

Why it is time to look beyond algal genes in photosynthetic slugs

Eukaryotic organelles depend on nuclear genes to perpetuate their biochemical integrity. This is true for mitochondria in all eukaryotes and plastids in plants and algae. Then how do kleptoplasts, plastids that are sequestered by some sacoglossan sea slugs, survive in the animals' digestive gland cells in the absence of the algal nucleus encoding the vast majority of organellar proteins? For almost two decades, lateral gene transfer (LGT) from algae to slugs appeared to offer a solution, but RNA-seq analysis, later supported by genome sequencing of slug DNA, failed to find any evidence for such LGT events. Yet, isolated reports continue to be published and are readily discussed by the popular press and social media, making the data on LGT and its support for kleptoplast longevity appear controversial. However, when we take a sober look at the methods used, we realize that caution is warranted in how the results are interpreted. There is no evidence that the evolution of kleptoplasty in sea slugs involves LGT events. Based on what we know about photosystem maintenance in embryophyte plastids, we assume kleptoplasts depend on nuclear genes. However, studies have shown that some isolated algal plastids are, by nature, more robust than those of land plants. The evolution of kleptoplasty in green sea slugs involves many promising and unexplored phenomena, but there is no evidence that any of these require the expression of slug genes of algal origin