PD-1 B cell

Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are endogenous lipids that act as agonists of the peroxisome proliferator-activated receptor α (PPARα). Recently, an interest in the role of these lipids in malignant tumors has emerged. Nevertheless, the effects of OEA and PEA on human neuroblastoma cells are still not documented. Type I interferons (IFNs) are immunomodulatory cytokines endowed with antiviral and anti-proliferative actions and are used in the treatment of various pathologies such as different cancer forms (i...

HBV is the most common risk factor for HCC development, accounting for almost 50% of cases worldwide. Despite significant advances in immunotherapy, there is limited information on the HBV-HCC tumor microenvironment (TME), which may influence the response to checkpoint inhibitors. Here, we characterize the TME in a unique series of liver specimens from HBV-HCC patients to identify who might benefit from immunotherapy. By combining an extensive immunohistochemistry analysis with the transcriptomic profile of paired liver samples (tumor vs...

Understanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson's disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chambered microfluidic platform and established a cortico-striato-nigral microcircuit partially recapitulating the striatal presynaptic landscape in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, cortical glutamatergic projections facilitated MSN synaptic activity, and dopaminergic transmission enhanced maturation of MSNs in vitro...

Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized treatment for relapsed/refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL). Robust biomarkers and a complete understanding of CAR-T cell function in the post-infusion phase remain limited. Here we used a 37-color spectral flow cytometry panel to perform high dimensional single cell analysis of post-infusion samples in 26 patients treated with CD28 co-stimulatory domain containing commercial CAR-T (CD28-CAR-T) for NHL and focused on computationally gated CD8+ CAR-T cells...

Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood...

BACKGROUND: Cross-reactive SARS-CoV-2-specific memory CD4+ and CD8+ T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4+ and CD8+ T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. METHODS: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4+ and CD8+ T cells between common cold coronaviruses (CCCs) and SARS-CoV-2...

In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells...

Stage IIIA-N2 non-small cell lung cancer (NSCLC) is a heterogeneous group with different potential therapeutic approaches. Treatment is typically multimodal with either surgical resection after neoadjuvant chemotherapy and/or radiation or concurrent chemotherapy and radiation if unresectable. Despite the multimodal treatment and early stage, cure rates have traditionally been low. The introduction of immunotherapy changed the treatment landscape for NSCLC in all stages, and the introduction of immunotherapy in early-stage lung cancer has improved event free survival and overall survival...

Sweet potato (Ipomoea batatas [L.] Lam.) is a versatile crop, cultivated in the subtropical and tropical areas, as food, fodder, and industrial raw material crop. In China, sweet potato has been used as a health-care food in recent years, as it contains a wide range of nutrients and xenobiotic phytochemicals. However, viral diseases are major constraint for the sweet potato yield and quality, especially the seed production and quality. Over 30 species of viruses infect sweet potato worldwide (Clark et al. 2012)...

Cancer immunotherapy based on bioengineering of bacteria can effectively increase anticancer immune responses. However, few studies have investigated the antitumor potential of engineering Proteus mirabilis . Here, we genetically engineered P. mirabilis to overexpress Vibrio vulnificus flagellin B (FlaB) protein in a murine CT26 tumor model. We found that a large number of FlaB-expressing P. mirabilis colonized tumor tissues, enhanced T cell infiltration and secretion of cytokines and cytotoxic proteins in tumors, and significantly restrained tumor growth...

The balance between T helper 1 (Th1) and T helper 2 (Th2) has a critical function in determining intratumoral immune response and anti-PD-1 immunotherapy. The level of maternal embryonic leucine zipper kinase (MELK) is reported to correlate with infiltration of immune cells in cancers, but the underlying molecular mechanism is not clarified. In the present study, we aimed to elucidate the potential function of MELK in cervical cancer. We found that MELK was upregulated and played an oncogenic role in cervical cancer...

Background: HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells...

Hepatitis B virus (HBV) infection generally elicits weak type-I interferon (IFN) immune response in hepatocytes, covering the regulatory effect of IFN-stimulated genes. In this study, low level of IFN-stimulated gene 12a (ISG12a) predicted malignant transformation and poor prognosis of HBV-associated hepatocellular carcinoma (HCC), whereas high level of ISG12a indicated active NK cell phenotypes. ISG12a interacts with TRIM21 to inhibit the phosphorylation activation of protein kinase B (PKB, also known as AKT) and β-catenin, suppressing PD-L1 expression to block PD-1/PD-L1 signaling, thereby enhancing the anticancer effect of NK cells...

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative and polygenic disorder characterised by the progressive loss of neural dopamine and onset of movement disorders. We previously described eight SINE-VNTR-Alu (SVA) retrotransposon-insertion-polymorphisms (RIPs) located and expressed within the Human Leucocyte Antigen (HLA) genomic region of chromosome 6 that modulate the differential co-expression of 71 different genes including the HLA classical class I and class II genes in a Parkinson's Progression Markers Initiative (PPMI) cohort...

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway...

BACKGROUND: Despite the encouraging outcome of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) in managing relapsed or refractory multiple myeloma (RRMM) patients, the therapeutic side effects and dysfunctions of CAR-T cells have limited the efficacy and clinical application of this promising approach. METHODS: In this study, we incorporated a short hairpin RNA cassette targeting PD-1 into a BCMA-CAR with an OX-40 costimulatory domain...

Chronic destruction of insulin-producing pancreatic β cells by T cells results in autoimmune diabetes. Similar to other chronic T cell-mediated pathologies, a role for T cell exhaustion has been identified in diabetes in humans and NOD mice. The development and differentiation of exhausted T cells depends on exposure to Ag. In this study, we manipulated β cell Ag presentation to target exhausted autoreactive T cells by inhibiting IFN-γ-mediated MHC class I upregulation or by ectopically expressing the β cell Ag IGRP under the MHC class II promotor in the NOD8...

The stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity and therefore plays an important role in cancer immune surveillance. This has prompted widespread development of STING agonists for cancer immunotherapy, but pharmacological barriers continue to limit the clinical impact of STING agonists and motivate the development of drug delivery systems to improve their efficacy and/or safety. To address this challenge, we developed SAPCon, a STING-activating polymer-drug conjugate platform based on strain-promoted azide-alkyne cycloaddition of dimeric-amidobenzimidazole (diABZI) STING agonists to hydrophilic polymer chains through an enzyme-responsive chemical linker...

Programmed cell death protein 1 (PD-1) inhibitors have modest efficacy as a monotherapy in hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) may enhance responses to PD-1 inhibitors through the induction of tumor-specific immunity. We present results from a single-arm, open-label, phase 1/2 study of a DNA plasmid PTCV (GNOS-PV02) encoding up to 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab in patients with advanced HCC previously treated with a multityrosine kinase inhibitor...

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