Tumor Immune Microenvironment and Immunotherapy in Non-Small Cell Lung Cancer: Update and New Challenges

BackgroundCholangiocarcinoma is a prevalent gastrointestinal tumor with limited effective early diagnostic methods. The role of neutrophils in the context of cholangiocarcinoma remains largely unexplored.MethodsA comprehensive analysis was performed on a cohort of cholangiocarcinoma samples (TCGA‐CHOL) from the TCGA database to investigate the relationship between cholangiocarcinoma and neutrophils. Methodologies included single‐sample gene set enrichment analysis (ssGSEA), differential expression analysis, weighted gene co‐expression network analysis (WGCNA) and gene set enrichment analysis (GSEA).ResultsThe study identified a significant decrease of neutrophils in cholangiocarcinoma via ssGSEA. WGCNA and differential expression analysis led to the identification of a neutrophil‐related gene module comprised of 1059 genes. Cluster 1, showing a higher proportion of neutrophils, was linked to better survival outcomes. GSEA disclosed downregulation of complement, inflammatory response and interferon response pathways in Cluster 2, hinting at possible cholangiocarcinoma development triggers. A notable upregulation of PD1, PD‐L1 and CTLA4 was observed in Cluster 1, suggesting potential benefits from immunotherapy. A prognostic model was developed based on clinical data and expression levels of three prognostic genes (SOWAHD, TNFAIP8 and EBF3) showing satisfactory discrimination, calibration and clinical benefits. An overexpression of TNFAIP8 in cholangiocarcinoma cells was found, with its knockdown significantly inhibiting cell proliferation and migration.ConclusionsThis study elucidates a neutrophil‐related gene module and prognostic genes, offering insights into the role of neutrophils in cholangiocarcinoma development and progression. It also introduces a clinical prediction model for enhanced prognosis assessment. These findings may lay the groundwork for the development of innovative therapeutic strategies in cholangiocarcinoma treatment.

Section: Introductionmentioning

confidence: 99%

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

Xiong

Wang

et al. 2023

“…To the best of our knowledge, ICBs developed to target immune checkpoint genes have shown promise in some patients. 37 The use of nanomaterials can be combined with anti-tumor drugs to kill tumors, and can also be designed to boost the body's own immunity to achieve the effect of multiple treatments. 38,39 The results of this study show that the UPS score could predict different degrees of immune microenvironment, suggesting the possibility of precision immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Development of an ubiquitin‐proteasome system signature for predicting prognosis and providing therapeutic guidance for patients with triple‐negative breast cancer

Chen,

Ren,

Zhou

et al. 2023

BackgroundTriple‐negative breast cancer (TNBC) is a pathological subtype with a high mortality, and the development of inhibitors in the ubiquitin–proteasome system (UPS) component could be a novel therapeutic tool.MethodsTriple‐negative breast cancer data were obtained from The Cancer Genome Atlas (TCGA), and subtype analysis was performed by consistent clustering analysis to identify molecular subtypes of TNBC according to UPS characteristics. Differential analysis, COX and least absolute shrinkage and selection operator (LASSO) COX regression analyses were performed to select genes associated with overall survival in TNBC. The final prognostic model (UPS score) was determined using the LASSO COX model. The model performance was assessed using receiver operating characteristic (ROC) curves and survival curves. In addition, the results of the UPS score on analyzing the abundance of immune cell infiltration and immunotherapy were explored. Finally, we developed a nomogram for TNBC survival prediction.ResultsTwo UPS subtypes (UPSMS1 and UPSMS2) showing significant survival differences were classified. COX regression analysis on differentially expressed genes in UPSMS1 and UPSMS2 filtered five genes that affected overall survival. Based on the regression coefficients and expression data of the five genes, we built a prognostic assessment system (UPS score). The UPS score showed consistent prognostic and therapeutic guidance values. Finally, the ROC curve of the nomogram and UPS score showed the highest predictive efficacy compared with traditional clinical prognostic indicators.ConclusionThe UPS score represented a promising prognostic tool to predict overall survival and immune status and guide personalized treatment selection in TNBC patients, and this study may provide a more practical alternative for clinical monitoring and management of TNBC.

“…20,21 The advent of immunotherapy has opened up new directions in the management of tumours, with the aim of inducing or restoring the function of immune cells to recognise and kill tumour cells and to generate a sustained anti-tumour immune response as well as increasing the number of immune cells that infiltrate into the tumour. [22][23][24] Immunotherapy not only improves the survival of tumour patients, but also has fewer side effects than conventional chemotherapy and can be combined with chemotherapy to enhance its benefits. Immunotherapy against immune checkpoint inhibitors such as PD-1/PD-L1 has been used as a first-and second-line treatment for non-small cell lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Machine learning reveals PANoptosis as a potential reporter and prognostic revealer of tumour microenvironment in lung adenocarcinoma

Han,

Danzeng,

et al. 2023

Lung adenocarcinoma (LUAD), a prominent lung cancer subtype, has an underexplored relationship with PANoptosis, a recently discovered mode of tumour cell death. This study incorporated iron death, copper death, scorch death, necrotizing apoptosis and bisulfide death into a pan‐death gene set (PANoptosis) and conducted single‐cell analysis of scRNA‐seq data from 11 LUAD samples. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Univariate COX regression and least absolute shrinkage and selection operator (LASSO) regression were used to screen PANoptosis key genes for constructing an LUAD risk model. The model’s prognostic performance was evaluated using survival curves, risk scores and validation in the Gene Expression Omnibus database. The study also explored the correlation between risk scores, tumour biological function, immunotherapy, drug sensitivity and immune infiltration. The SMS gene in the PANoptosis model was silenced in two LUAD cell lines for cellular validation. Single‐cell analysis revealed eight major cell types and several PANoptosis genes significantly associated with LUAD survival. The risk model demonstrated strong prognostic performance and association with immune infiltration, suggesting PANoptosis involvement in LUAD tumour immunity. Cellular validation further supported these findings. The PANoptosis key risk genes are believed to be closely related to the tumour microenvironment and immune regulation of LUAD, potentially providing valuable insights for early diagnosis and clinical treatment, and broader applications in other tumours and complex diseases.