LAMP1 (Lysosomal Associated Membrane Protein 1)

In particular, HLA-B leader matched patients had a higher CD57 expression of total NK and NKG2A+KIR- NK cells, with enhanced NKG2A+KIR- NK cell cytotoxicity (CD107a expression) and IFN-γ secretion at 1, 3, and 6 months post-transplantation (all false discovery rate-adjusted P <0.05). These findings identify HLA-B leader matching status as a disease-specific prognostic biomarker, suggesting its potential relevance for personalized donor selection considerations in haplo-HSCT settings.

The Fc-optimized anti-CD276 antibody 8H8_SDIE effectively enhanced NK cell reactivity against CD276-positive CRC cells and induced tumor cell lysis in vitro. These findings suggest that 8H8_SDIE holds potential as a novel immunotherapeutic candidate for CRC, particularly for patients with microsatellite-stable disease, and warrants further evaluation in advanced preclinical and future clinical studies.

The presence of DAO in peroxisomes, autophagosomes, lysosomes, and exosomes indicated diverse intracellular localization within CPECs. This distribution may enable efficient metabolism of blood-derived D-serine in CPECs.

To maximize the immunotherapeutic efficacy of PDT, we developed a photodynamic immunotherapeutic liposomal nanoplatform (PDIT-liposome) integrating components targeting sequential stages of the antitumor immune response: 1) a phthalocyanine photosensitizer to induce ICD, 2) a factor Xa inhibitor (rivaroxaban) to promote T-cell priming, 3) and a program death-ligand 1 inhibitor to augment cytotoxic T lymphocyte (CTL) attack... This study presents a strategy to amplify PDT-elicited immunotherapeutic efficacy by synergizing agents targeting distinct stages of the immune response. It also theoretically validates the synergy of PDT, anticoagulation therapy, and immune checkpoint inhibition in cancer treatment.

All together these data show that OCs negatively affect the NK cell cytotoxic activity, allowing the growth of NSCLC CSCs. Our findings reveal a previously unrecognized role of OCs in modulating the immune microenvironment by dampening NK cell function.

The GADEKILL γδ T and NK cells were analyzed by flow cytometry for the expression of activating and inhibitory receptors and for cytotoxicity against NB, both with and without dinutuximab-β, at a 1:1 effector-to-target ratio...Finally, NB cell lysis positively correlated with B7H6 and BTN2A1, and B7H6-blocking experiments revealed a significant decrease in target cell lysis when cells highly expressing B7H6 were used as targets. Our study demonstrated the potential antineuroblastoma activity of the GADEKILL, supporting its therapeutic use, particularly in the context of relapsed/refractory R/R HR-NB with low GD2 expression.

We successfully developed TIPE2-downregulated NKG2D-CAR-T cells that exhibited enhanced activation and cytotoxicity while limiting apoptosis and exhaustion against NKG2D ligand-expressing pancreatic tumors, highlighting TIPE2 as a promising intracellular immune checkpoint target for optimizing CAR-T cell therapy in solid tumors.

In vivo, perivascular delivery of PDK4-IN-1 in the mouse carotid artery injury model significantly ameliorated neointimal hyperplasia. Inhibition of PDK4 perturbs pathological VSMC phenotypic switching, suppresses proliferation, promotes apoptosis and autophagy, and mitigates neointimal formation, highlighting PDK4 as a promising therapeutic target for vascular proliferative diseases.

It suppressed Aβ and tau fibrillation, downregulated Bax and Caspase, upregulated Bcl2, Beclin-1, LC3B-II, and LAMP1, and reduced IL-6, TNF-α, and GSK3β expression, indicating potent neuroprotective, antioxidant, and anti-inflammatory effects.ConclusionsOverall, the results imply that Persicaria hydropiper exhibits protective activity on neuroblastoma cell lines by mitigating oxidative stress, Aβ/tau fibrils, cell death, and inflammation while also inducing autophagy induced by Aβ1-42. Further in vivo studies are needed to validate the findings to establish the plant as a potential source of anti-Alzheimer's drug.

Our findings demonstrate that MAP3K19 drives hypopharyngeal cancer progression by crippling DC activation, maturation, and function. MAP3K19 orchestrates DC dysfunction by phosphorylating and inactivating GSK3β, which simultaneously suppresses the NF-κB pathway and enhances PD-L1 protein stability. Targeting the MAP3K19/GSK3β axis may represent a novel therapeutic strategy to reverse immunosuppression in hypopharyngeal cancer.

Mechanistic studies revealed that E46K/DOPAC aggregates were preferentially degraded via the ubiquitin-proteasome system (UPS), as proteasome inhibition with MG132 enhanced toxicity and intracellular accumulation. In contrast, autophagy inhibition by chloroquine paradoxically reduced toxicity, indicating redirection toward UPS-mediated degradation...Overall, our results demonstrate that DOPAC reshapes the biophysical and toxicological properties of Syn aggregates, especially E46K species, by promoting less harmful oligomers and enhancing proteostatic clearance. These findings highlight DOPAC as a promising modulator of Syn aggregation and pathology.

Clinically, high TIM3 expression correlated with shorter progression-free survival and an increased risk of tumour progression. Collectively, our findings delineate a state of NK cell immunosuppression and metabolic impairment in progressive HCC, potentially driven by glycolytic reprogramming and establish TIM3 as a critical marker and potential therapeutic target.