Research Progress on Factors of Immunotherapy Resistance in Non-Small Cell Lung Cancer

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(03), P. 846 - 852

Published: Jan. 1, 2025

Language: Английский

---

Integration of intratumoral and peritumoral CT radiomic features with machine learning algorithms for predicting induction therapy response in locally advanced non-small cell lung cancer

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 13, 2025

To extract intratumoral, peritumoral, and integrated intratumoral-peritumoral CT radiomic features, develop multi-source models using various machine learning algorithms to identify the optimal model, integrate clinical factors establish a nomogram for predicting therapeutic response induction therapy(IT) in locally advanced non-small cell lung cancer. This study included 209 patients with cancer (LA-NSCLC) who received IT as training cohort, an external validation cohort comprising 50 from another center. Radiomic features were extracted regions by manually delineating gross tumor volume (GTV) additional 3 mm surrounding area. Three algorithms—Support Vector Machine (SVM), XGBoost, Gradient Boosting—were employed construct each region. Model performance was evaluated metrics such Area Under Curve (AUC), confusion matrix, accuracy, precision, recall, F1 score. Finally, comprehensive integrating model independent predictors developed. Through comparison of algorithms, INTRAPERI, INTRA, PERI achieved best Boosting, SVM, respectively. Compared INTRA_SVM PERI_XGBoost INTRA models, fusion that integrates peritumoral within margin around (INTRAPERI_GradientBoosting) showed better predictive set, AUCs 93.7%, 82.5%, 89.4%, In PS score identified factor. The combining INTRAPERI_GradientBoosting demonstrated value. which intra-tumoral performs than radiomics efficacy therapy LA-NSCLC. Additionally, based on INTRAPERI combined has

Language: Английский

---

Efficacy and safety of induction immunochemotherapy followed by radiotherapy for patients with unresectable locally advanced non-small cell lung cancer: A retrospective study

Radiation Oncology, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 13, 2025

Immune checkpoint inhibitor (ICI) has displayed considerable advantages in consolidation therapy of locally advanced non-small cell lung cancer (LA-NSCLC) after concurrent chemoradiotherapy (cCRT). However, many patients are considered unsuitable for cCRT owing to concerns with tolerability. In this study, we aimed assess the efficacy and toxicity induction immunochemotherapy followed by radiotherapy unresectable LA-NSCLC who not capable receiving cCRT. From January 2019 December 2022, treated as initial treatment at our institution were retrospectively reviewed. The short-term efficacy, overall survival (OS), progression free (PFS) tolerability evaluated these patients. Overall, 24 enrolled (median age 64 years, 33.3% ECOG performance status score 2, 62.5% stage IIIB-IIIC). Median follow-up from start was 30.5 months. number 4 cycles. A median dose 60 Gy delivered. After radiotherapy, 16 (66.6%) received immunotherapy. response rate 87.5%. 1-year, 2-year 3-year OS 91.7%, 74.8% 57.0%, respectively. PFS 87.0%, 54.1% 37.1%, incidence grade ≥ 2 3 pneumonitis 37.5% 16.7%, Radiation any occurred 8 (33.3%), radiation 16.7% 12.5%, Induction consolidated immunotherapy had encouraging acceptable

Language: Английский

---

Tumor treating fields enhance anti-PD therapy by improving CCL2/8 and CXCL9/CXCL10 expression through inducing immunogenic cell death in NSCLC models

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 17, 2025

Non-small cell lung cancer (NSCLC) is the most common type of cancer. Tumor treating fields (TTFields) combined with anti-PD immunotherapy offers a promising strategy to address this issue. Nevertheless, mechanism action (MOA) TTFields therapy in NSCLC has not been thoroughly investigated. This study aims elucidate MOA from aspect improving tumor immune microenvironment (TIME). Using mouse model NSCLC, we tested efficacy anti-PD-1 and anti-PD-L1 immunotherapy. By RNA-seq, differential genes signaling pathways between combination groups were studied. In-vitro experiments validated effects on cells for CD4+ T CD8+ infiltration, as well expression immunogenic death related chemokines. Combining reduced weight volume, respectively, compared controls (p < 0.05). RNA-seq analysis revealed 1,745 differentially expressed (DEGs) group versus controls, including upregulated (ICD) associated genes. Further showed that resulted increased infiltration alone, induced higher level ATP, HMGB1, CCL2, CCL8, CXCL9, CXCL10 inflammatory cytokines than control group. These collectively contributed altered TIME, finally potentiated therapy. enhance effectiveness by via inducing ICD increase CCL2/8 CXCL9/CXCL10 cells. provides theoretical basis new insights evaluating NSCLC.

Language: Английский

---

NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation

Open Life Sciences, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Radiotherapy (RT) resistance in non-small cell lung cancer (NSCLC) is a significant contributor to tumor recurrence. NAT10, an enzyme that catalyzes ac4C RNA modification, has unclear role RT resistance. This study aimed explore the function of NAT10 NSCLC. RT-resistant NSCLC lines (PC9R and A549R) were established through repeated irradiation. The impact on cellular immunity was evaluated by measuring immune populations, cytotoxicity levels, markers dysfunction. Results demonstrated elevated levels cells. Knockdown suppressed proliferation enhanced PC9R A549R cells upregulating TNF-α IFN-γ while downregulating PD-1 TIM-3. Mechanistically, mediated NAT10-dependent modification KPNB1. Furthermore, KPNB1 facilitated PD-L1 nuclear translocation, promoting escape Overexpression but impaired In conclusion, this demonstrates upregulates expression thereby via translocation. These findings reveal novel mechanism underlying

Language: Английский

---

Development of an alkaliptosis-related lncRNA risk model and immunotherapy target analysis in lung adenocarcinoma

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

Lung cancer has the highest mortality rate among all cancers worldwide. Alkaliptosis is characterized by a pH-dependent form of regulated cell death. In this study, we constructed model related to alkaliptosis-associated long non-coding RNAs (lncRNAs) and developed prognosis-related framework, followed identification potential therapeutic drugs. The TCGA database was utilized obtain RNA-seq-based transcriptome profiling data, clinical information, mutation data. We conducted multivariate Cox regression analysis identify alkaliptosis-related lncRNAs. Subsequently, employed training group construct prognostic testing validate model's accuracy. Calibration curves were generated illustrate discrepancies between predicted observed outcomes. Principal Component Analysis (PCA) performed investigate distribution LUAD patients across high- low-risk groups. Additionally, Gene Ontology (GO) Set Enrichment (GSEA) conducted. Immune infiltration Tumor Mutational Burden (TMB) analyses carried out using CIBERSORT maftools algorithms. Finally, "oncoPredict" package predict immunotherapy sensitivity further forecast anti-tumor immune qPCR used for experimental verification. identified 155 lncRNAs determined that 5 these serve as independent factors. progression-free survival (PFS) overall (OS) rates significantly higher than those high-risk group. risk signature functions factor other variables. Different stages (I-II III-IV) effectively lung adenocarcinoma (LUAD) patients, can reliably signatures. GSEA revealed processes chromosome segregation response activation enriched in both exhibited lower fraction plasma cells proportion activated CD4 memory T cells. OS low TMB compared high Furthermore, drug greater These may biomarkers treating patients. summary, construction an lncRNA provides new insights into diagnosis treatment advanced

Language: Английский

---

Raddeanin A exerts potent efficacy against non-small cell lung cancer by inhibiting cyclin-dependent kinase 6

Translational Oncology, Journal Year: 2025, Volume and Issue: 56, P. 102382 - 102382

Published: April 11, 2025

Language: Английский

---

RAF1 promotes anlotinib resistance in non-small cell lung cancer by inhibiting apoptosis

Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(4)

Published: April 14, 2025

Language: Английский

---

MYCN/MNX1 Axis Drives NSCLC Progression by Inducing Macrophage M2 Polarization and CD8⁺ T Cell Apoptosis via the Wnt/β‐Catenin Pathway

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(4)

Published: April 1, 2025

ABSTRACT Enhanced macrophage M2 polarization and CD8 + T cell dysfunction contribute to the pathophysiology of non‐small lung cancer (NSCLC). Motor neuron pancreatic homeobox 1 (MNX1) has emerged as a potential tumor‐promoting player. Here, we clarified activity MNX1 in NSCLC. PMA‐induced THP‐1 M0‐like macrophages or cells were co‐cultured with NSCLC cells. Cell colony formation, migration, proliferation, apoptosis, invasiveness assessed by wound healing, CCK‐8, flow cytometry, transwell assays, respectively. The ratio CD206 was analyzed cytometry. Ki‐67 expression tested immunofluorescence. ChIP luciferase assays used evaluate relationship between MYCN MNX1. highly expressed NSCLC, its loss‐of‐function suppressed growth, motility, depletion also diminished apoptosis. Mechanistically, increased at transcriptional level. increase reversed impact on malignant behaviors, polarization, viability. vivo growth A549 subcutaneous xenografts. Additionally, counteracted Wnt/β‐catenin pathway. Our findings elucidate oncogenic role MYCN/MNX1/Wnt/β‐catenin pathway driving diminishing study thus uncovers novel mechanism underlying development highlights targets for combating

Language: Английский

---

Engineered lung cell targeting and SLC7A11 siRNA expressing bacterial extracellular vesicles impair the progression of none‐small cell lung cancer

Bioengineering & Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Non‐small cell lung cancer (NSCLC) presents significant therapeutic challenges, often characterized by aggressive proliferation and metastasis. This study investigates the role of SLC7A11, a ferroptosis‐related gene, in NSCLC progression potential engineered bacterial extracellular vesicles (BEVs) expressing SLC7A11‐targeting siRNA as strategy. Using TCGA GEO databases, we identified that SLC7A11 was significantly upregulated tissues. Functional assays demonstrated knockdown lines (NCI‐H2122 NCI‐H647) via qPCR, Western blot, immunofluorescence resulted impaired proliferation, migration, invasion abilities. In vivo xenograft models further revealed inhibited tumor growth metastasis, corroborated histological analyses. To enhance targeted delivery siRNA, BEVs with targeting peptide, verifying their structure function through transmission electron microscopy (TEM) nanoparticle tracking analysis (NTA). toxicity assessments indicated safety for these bioengineered vesicles. Importantly, treatment BEVs‐LCTP‐siSLC7A11 not only tumorigenesis but also activated ferroptosis pathways, evidenced altered expression levels transferrin metastatic Our findings suggest promising approach to inhibit while activating ferroptosis, offering insights into novel strategies against cancer.

Language: Английский

---