Pancreatic adenocarcinoma (PAAD) is a common, highly malignant, and aggressive gastrointestinal tumor. The conventional treatment of PAAD shows poor results, and patients have poor prognosis. The synthesis and degradation of proteins are essential for the occurrence and development of tumors. Aggrephagy is a type of autophagy that selectively degrades aggregated proteins. It decreases the formation of aggregates by degrading proteins, thus reducing the harm to cells. By breaking down proteins, it decreases the formation of aggregates; thus, minimizing damage to cells. For evaluating the response to immunotherapy and prognosis in PAAD patients, in this study, we developed a reliable signature based on aggrephagy-related genes (ARGs). We obtained 298 AGGLncRNAs. Based on the results of one-way Cox and LASSO analyses, the lncRNA signature was constructed. In the risk model, the prognosis of patients in the low-risk group was noticeably better than that of the patients in the high-risk group. Additionally, the ROC curves and nomograms validated the capacity of the risk model to predict the prognosis of PAAD. The patients in the low-risk and high-risk groups showed considerable variations in functional enrichment and immunological analysis. Regarding drug sensitivity, the low-risk and high-risk groups had different half-maximal inhibitory concentrations (IC50).

Bronchial asthma is divided into Th2 high, Th2 low and mixed types. The Th2 high type is dominated by eosinophils while the Th2 low type is divided into neutrophilic and paucigranulocytic types. Eosinophilic asthma has gained increased attention recently, and its pathogenesis and treatment are well understood. However, severe neutrophilic asthma requires more in‐depth research because its pathogenesis is not well understood, and no effective treatment exists. This review looks at the advances made in asthma research, the pathogenesis of neutrophilic asthma, the mechanisms of progression to severe asthma, risk factors for asthma exacerbations, and biomarkers and treatment of neutrophilic asthma. The pathogenesis of neutrophilic asthma is further discussed from four aspects: Th17‐type inflammatory response, inflammasomes, exosomes and microRNAs. This review provides direction for the mechanistic study, diagnosis and treatment of neutrophilic asthma. The treatment of neutrophilic asthma remains a significant challenge for clinical therapists and is an important area of future clinical research.

Background: Sialic acid-binding immunoglobulin-type lectin (SIGLEC) family members are involved in regulating immune-cell activation, proliferation, and apoptosis, and they play an important role in tumor development. However, their expression and correlation with immune molecules in lung adenocarcinoma (LUAD) remain unclear.Methods: We utilized Gene Expression Profiling Interactive Analysis, Kaplan–Meier analysis, the limma package in R/Bioconductor, the University of California Santa Cruz Cancer Genome Browser, cBioPortal, STRING, Cytoscape, DAVID, and the Tumor Immune Estimation Resource for gene and protein profiling and analyses.Results: The results showed that SIGLEC10 and SIGLEC15 levels were upregulated in LUAD, whereas SIGLEC1, CD22 (SIGLEC2), CD33, myelin-associated glycoprotein (SIGLEC4), SIGLEC5, SIGLEC6, SIGLEC7, SIGLEC8, SIGLEC11, and SIGLEC14 levels were significantly downregulated, with their low expression associated with poor overall survival. Moreover, we observed high SIGLEC-mutation rates (22%) in LUAD patients, with SIGLEC functions determined as primarily involved in regulating the immune response, signal transduction, inflammatory response, and cell adhesion. Furthermore, we found that SIGLEC expression was significantly correlated with immune-cell infiltration, especially macrophages, neutrophils, and dendritic cells, and highly associated with immune molecules such as CD80, CD86, CD28, B-cell-activating factor, programmed cell death 1 ligand 2, and colony stimulating factor 1 receptor.Conclusion: These results provide insight into the potential molecular mechanism associated with SIGLEC-related development of LUAD, as well as clues for screening biomarkers and therapeutic targets.

Objective: Given the limitations of immunotherapy for treating non-small cell lung cancer (NSCLC), we investigated the phenotype and function of exhausted CD8⁺T cells and analyzed a novel combination immunotherapy to restore the effector killing function of tumor-infiltrating CD8⁺T lymphocyte (TIL).Methods: We examined the expression and function of immunosuppressive molecules on CD8⁺T cells of peripheral blood mononuclear cells (PBMCs) and TILs by using prospectively collected peripheral blood, pleural effusions, and tumor tissues from patients with NSCLC and correlated the results with clinical data. We then evaluated the effect of interleukin 6 (IL-6) stimulation on CD8⁺T cells. Finally, we assessed the effects of combined blockade of PD1 and IL-6 on macrophage recruitment in a zebrafish macrophage model and CD8⁺ T cell function and tumor growth in PBMC humanized mouse model.Results: The expression of exhaustion markers on CD8⁺ T cells was found to be notably higher in both tumor and paraneoplastic tissues compared to peripheral blood. Furthermore, the degree of CD8⁺ T cell exhaustion exhibited a progressive increase with proximity to the tumor. When CD8⁺ T cells from peripheral blood and tumor tissues of NSCLC patients were stimulated with IL-6, the expression level of exhaustion markers, especially PD1, was further elevated. In the in vitro experiment, the combined inhibition of IL-6 and PD1 substantially enhanced the effector killing function of CD8⁺ T cells in NSCLC pleural effusion samples. In a macrophage-labeled zebrafish model, combined blockade of IL-6 and PD1 enhanced the recruitment of macrophages. In PBMC humanized mouse model, combined blockade of IL-6 and PD1 enhanced the inhibition of tumor growth.Conclusion: Our data suggest that CD8⁺ T cells in NSCLC patients were in a state of exhaustion and combined blockade of IL-6 and PD1 to restore CD8⁺ T cell function to inhibit tumor growth may be an effective clinical strategy for the treatment of NSCLC.