This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Lung cancer is a fatal disease with the highest worldwide morbidity and mortality rates. Despite recent advances in targeted therapy and immune checkpoint inhibitors for cancer, their efficacy remained limited. Therefore, we designed a Newcastle disease virus (NDV)‐modified tumor whole‐cell vaccine as a therapeutic vaccine and identified its antigen presentation level to develop effective immunotherapy. Then, we calculated the therapeutic and immune‐stimulating effects of NDV‐modified lung cancer cell vaccine and intratumoral NDV injection combination on tumor‐bearing mice. The results showed that the immunogenic cell death (ICD) expression in NDV‐modified lung cancer cell vaccine stimulates dendritic cell maturation and T cell activation in vivo and in vitro. Moreover, NDV‐modified lung cancer cell vaccine combined with intratumoral NDV injection could significantly inhibit tumor growth and enhance the differentiation of Th1 cells and Inflammatory cell infiltration in vivo, leading to an excellent immunotherapeutic effect. Therefore, our results revealed that NDV‐modified lung cancer cell vaccine combined with intratumoral NDV injection could promote antigen presentation and induce a strong antitumor immune response, which provided a promising combined therapy strategy for tumor immunotherapy.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Lung adenocarcinoma (LUAD) is the most common type of lung cancer and the leading cause of cancer incidence and mortality worldwide. Despite the improvement of traditional and immunological therapies, the clinical outcome of LUAD is still far from satisfactory. Patients given the same treatment regimen had different responses and clinical outcomes due to the heterogeneity of LUAD. How to identify the targets based on heterogeneity analysis is crucial for treatment strategies. Recently, the single-cell RNA-sequencing (scRNA-seq) technology has been used to investigate the tumor microenvironment (TME) based on cell-specific changes and shows prominently valuable for biomarker prediction. In this study, we systematically analyzed a meta-dataset from the multiple LUAD scRNA-seq datasets in LUAD, identified 15 main types of cells and 57 cell subgroups, and revealed a series of potential biomarkers in M2b, exhausted CD8+T, endothelial cells, fibroblast, and metabolic patterns in TME, which further validated with immunofluorescence in clinical cohorts of LUAD. In the prognosis analysis, M0 macrophage and T cell activation were shown correlated to a better prognosis (p<0.05). Briefly, our study provided insights into the heterogeneity of LUAD and assisted in novel therapeutic strategies for clinical outcome improvement.
Background
Glioma is the most common intracranial malignancy with a poor prognosis. Although remarkable advances have been made in the study of diagnostic and prognostic biomarkers, the efficacy of current treatment strategies is still unsatisfactory. Therefore, developing novel and reliable targets is desperately needed for glioma patients. Pyroptosis reshapes tumor immune microenvironment (TME) and promotes the destruction of the tumor by the immune system. Moreover, pyroptosis levels correlate with prognosis and immunotherapy response in many cancer patients. This study performed a comprehensive analysis of pyroptosis in the glioma, unveiling its potential value in glioma prognosis prediction and therapy efficacy.
Methods
Firstly, the pyroptosis regulation patterns were comprehensively evaluated on 33 pyroptosis-related genes in 1716 glioma samples. The correlations were analyzed between pyroptosis regulation patterns and TME immune cell infiltration properties. Next, pyroptosis regulation patterns were measured by the PSscore model based on principal component analysis algorithms. The correlations were analyzed between PSscore and tumor mutational burden (TMB), immune checkpoint blockade (ICB) therapeutic advantages. Last, the findings were validated in an independently collected external clinical cohort.
Results
We determined two distinct pyroptosis regulation patterns. The cluster-A was high immune cell infiltration with a poor prognosis (p < 0.001), whereas the cluster-B was low immune cell infiltration with a better prognosis (p < 0.001). We developed the PSscore as a measure for pyroptosis regulation patterns. The high PSscore with an inflamed TME phenotype, a high TMB (p < 0.0001), increased innate immune response, and a poor prognosis (p < 0.001). It was in stark contrast to the low PSscore (p < 0.001). Analysis of PSscore with checkpoint therapy indicated high PSscore were correlated with enhanced response to anti-PD-1 immunotherapy (p = 0.0046). For validation, we utilized in vitro experiments on an external clinical cohort. The results demonstrated that GSDMD expression level in the high PSscore group was significantly upregulated compared to the low PSscore group (p < 0.001); the CD3+ T cells and the CD3+PD-1+ cells significantly increased in the high PSscore group compared to the low PSscore group (p < 0.01).
Conclusions
The PSscore of pyroptosis regulation pattern is a reliable biomarker, and it is valuable to predict prognosis, TME, and ICB therapeutic efficiency in glioma patients.
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