Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction plays a crucial role in tumor-associated immune escape. Here, we verify that triple-negative breast cancer (TNBC) has higher PD-L1 expression than other subtypes. We then discover that nucleophosmin (NPM1) binds to PD-L1 promoter specifically in TNBC cells and activates PD-L1 transcription, thus inhibiting T cell activity in vitro and in vivo. Furthermore, we demonstrate that PARP1 suppresses PD-L1 transcription through its interaction with the nucleic acid binding domain of NPM1, which is required for the binding of NPM1 at PD-L1 promoter. Consistently, the PARP1 inhibitor olaparib elevates PD-L1 expression in TNBC and exerts a better effect with anti-PD-L1 therapy. Together, our research has revealed NPM1 as a transcription regulator of PD-L1 in TNBC, which could lead to potential therapeutic strategies to enhance the efficacy of cancer immunotherapy.

Inflammation plays a critical role in the development of severe neonatal morbidities. Myeloid-derived suppressor cells (MDSCs) were recently implicated in the regulation of immune responses in newborns. Here, we report that the presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum. Low amounts of MDSCs at birth predicted the development of severe pathology in preterm infants — necrotizing enterocolitis (NEC). In vitro treatment of newborn neutrophils and monocytes with LF converted these cells to MDSCs via the LRP2 receptor and activation of the NF-κB transcription factor. Decrease in the expression of LRP2 was responsible for the loss of sensitivity of adult myeloid cells to LF. LF-induced MDSCs (LF-MDSCs) were effective in the treatment of newborn mice with NEC, acting by blocking inflammation, resulting in increased survival. LF-MDSCs were more effective than treatment with LF protein alone. In addition to affecting NEC, LF-MDSCs demonstrated potent ability to control ovalbumin-induced (OVA-induced) lung inflammation, dextran sulfate sodium–induced (DSS-induced) colitis, and concanavalin A–induced (ConA-induced) hepatitis. These results suggest that cell therapy with LF-MDSCs may provide potent therapeutic benefits in infants with various pathological conditions associated with dysregulated inflammation.

Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway

The morbidity of atopic diseases and disorders of immune dysregulation like asthma, food allergy, multiple sclerosis, atopic dermatitis, type Ⅰ diabetes mellitus, and inflammation bowel disease have been noticed increasing all around the world in the past decades. Though the roles of environmental factors and changes of genetic factors were particularly emphasized in etiopathology, they cannot exclusively explain the whole reason since they all need a long-term change. Epidemiological investigation has found that this increase also parallels with a decrease in infectious diseases especially the parasite infection. Thus, lowering prevalence of parasite infection may be another important reason for immune dysregulation . Parasites have co-evolved with the human immune system for a long time. Some immune-evasion molecules from parasites have been verified to reduce the incidence and harmfulness of atopic diseases by modulation the human immune responses. More important, some parasite-derived products are proved to inhibit the progression of inflammatory diseases and consequently alleviate the symptoms of inflammatory diseases. Thus, parasite especially their products may have potential applications in treatment of autoimmune diseases. In the review, therapeutic potential of the parasite-derived products and their analogues for the atopic diseases and immune dysregulation were summarized.

Intravenous arsenic trioxide (ATO) has been adopted as the first‐line treatment for acute promyelocytic leukemia (APL). Another arsenic compound named the Realgar‐Indigo naturalis formula (RIF), an oral traditional Chinese medicine containing As₄S₄, has been shown to be highly effective in treating adult APL. In the treatment of pediatric APL, the safety and efficacy of RIF remains to be confirmed. This randomized, multicenter, and noninferiority trial was conducted to determine whether intravenous ATO can be substituted by oral RIF in the treatment of pediatric APL. From September 2011 to January 2017, among 92 patients who were 16 years old or younger with newly diagnosed PML‐RARa positive APL, 82 met eligible criteria and were randomly assigned to ATO (n = 42) or RIF (n = 40) group. The remaining 10 patients did not fulfilled eligible criteria because five did not accept randomization, four died and one had hemiplegia prior to arsenic randomization due to intracranial hemorrhage or cerebral thrombosis. Induction and consolidation treatment contained ATO or RIF, all‐trans‐retinoic acid and low intensity chemotherapy. End points included event‐free survival (EFS), adverse events and hospital days. After a median 3‐year follow‐up, the estimated 5‐year EFS was 100% in both groups, and adverse events were mild. However, patients in the RIF group had significantly less hospital stay than those in the ATO group. This interim analysis shows that oral RIF is as effective and safe as intravenous ATO for the treatment of pediatric APL, with the advantage of reducing hospital stay. Final trial analysis will reveal mature outcome data.