CD47 cGAS

CD103+ DC is crucial for antitumor immune response. As a promising local therapy on cancers, nanosecond pulsed electric field (nsPEF) has been widely reported to stimulate anti-tumor immune response, but the underlying relationship between intratumoral CD103+ DC and nsPEF treatment remains enigmatic. Here, we focused on the behavior of CD103+ DC in response to nsPEF treatment and explored the underlying mechanism. We found that the nsPEF treatment led to the activation and accumulation of CD103+ DC in tumor...

PURPOSE/OBJECTIVE(S): Radioimmunotherapies that combine radiation with antibodies against the "don't eat me" signal CD47 show increasing promise. One opportunity to synergize RT with anti-CD47 is via the Stimulator of Interferon Genes (STING) pathway which facilitates potent immune responses to cytoplasmic DNA. Anti-CD47 should activate STING by increasing macrophage consumption of tumor DNA. However, tumor contents are destroyed in phagolysosomes. Listeria (L.) monocytogenes escape lysosomes by secreting a pore-forming protein Listeriolysin O (LLO)...

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53 mutated AML, we identified polo-like kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms and therapeutic potential in TP53 mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wildtype AML and was increased in TP53 mutated AML cell lines and primary samples...

Due to the immunosuppressive tumor microenvironment (ITM) resulting from tumor-associated macrophages (TAMs) and regulatory T cells, immune checkpoint blockade and vaccine therapies often lead to an inadequate immune response. Recently, cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING)-mediated innate immunity has emerged as a promising cancer therapeutic, as STING pathway activation could promote dendritic cells (DCs) maturation and tumor-specific cytotoxic T lymphocyte (CTL) and natural killer (NK) cell infiltration...

The aims of this study were to enhance the antitumour immunity in Epstein-Barr virus-associated gastric cancer (EBVaGC).We performed RNA-seq analysis to compare the differential expression genes between EBVaGC and EBV-negative gastric cancer (EBVnGC) patients. The expression levels of CD68, CD163 and CD47 were analyzed by immunohistochemistry. Different subsets of macrophages were investigated by a coincubation model. The effects of CD47 blockade were also detected. The expression levels of CD68, CD163 and CD47 were significantly higher in EBVaGC, and were associated with poor prognoses...

When used according to specific dose/fractionation schedules, focal radiotherapy can elicit a systemic anticancer immune response that limits the growth of distant, non-irradiated tumors. Recent data suggest that, at least in some settings, intratumoral macrophages can be educated by CD47 blockage to promote such an 'abscopal' response independent of CD8+ T cells.

BACKGROUND & AIMS: The CD47-signal regulatory protein α (SIRPα) axis inhibits dendritic cell (DC) phagocytosis and contributes to immune evasion. However, the behaviour of DCs and the potential crosstalk between DCs and natural killer (NK) cells in the hepatocellular carcinoma (HCC) microenvironment after CD47 blockade remain unclear. METHODS: The infiltration of CD103+ DCs and NK cells were analysed by immunohistochemistry and immunofluorescence in both human and murine HCC specimens...

Tumour cell phagocytosis by antigen presenting cells (APCs) is critical to the generation of antitumour immunity. However, cancer cells can evade phagocytosis by upregulating anti-phagocytosis molecule CD47. Here, we show that CD47 blockade alone is inefficient in stimulating glioma cell phagocytosis. However, combining CD47 blockade with temozolomide results in a significant pro-phagocytosis effect due to the latter's ability to induce endoplasmic reticulum stress response. Increased tumour cell phagocytosis subsequently enhances antigen cross-presentation and activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) in APCs, resulting in more efficient T cell priming...

Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs...