bims-meluca 2025-08-03 papers

Medicina (Kaunas). 2025 Jun 26. pii: 1160. [Epub ahead of print]61(7):

Prognostic Role of Inflammatory and Nutritional Indices in NSCLC Patients Treated with Immune Checkpoint Inhibitors: Retrospective, Multicenter, Turkish Oncology Group Study of Overall and Elderly Populations.

Background and Objectives: Despite advances in immunotherapy, predicting survival outcomes in patients with non-small-cell lung cancer (NSCLC) remains challenging. Inflammatory and nutritional indices such as the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Inflammatory Burden Index (IBI) have emerged as promising prognostic markers associated with overall survival (OS) in NSCLC patients. Materials and Methods: We retrospectively analyzed a total of 196 NSCLC patients treated with second-line nivolumab across multiple centers in Turkey. Of these, 101 patients aged ≥ 65 years were included in the elderly subgroup analysis. PNI, GNRI (in patients aged ≥ 65), and inflammation-based indices were calculated using pre-treatment laboratory values. ROC analysis determined optimal cut-off values. The Kaplan-Meier method and Cox proportional hazards models were used for survival analysis. Results: Median overall survival (OS) was 12.9 months in the full cohort and 12.1 months in patients aged ≥ 65. In univariate analysis, ECOG performance status (0-1), lower NLR (<3.3), lower PLR (<196.8), higher PNI (≥45.2), and higher GNRI (≥98.0) were significantly associated with longer OS. However, in the multivariate analysis adjusted for ECOG PS, NLR, PLR, and GNRI, only PNI remained an independent prognostic factor for OS in both the overall cohort [HR: 0.49, 95% CI: 0.26-0.92; p = 0.02] and elderly patients [HR: 0.45, 95% CI: 0.24-0.84; p = 0.01]. PNI is an independent prognostic biomarker for OS in NSCLC patients treated with immune checkpoint inhibitors. Conclusions: These findings support incorporating simple, cost-effective nutritional indices into clinical decision-making, particularly in elderly patients with NSCLC.

Keywords: geriatric nutritional risk index (GNRI); immune checkpoint inhibitors; inflammation-based indices; nivolumab; non-small-cell lung cancer (NSCLC); prognostic nutritional index (PNI)

DOI: https://doi.org/10.3390/medicina61071160

Discov Oncol. 2025 Jul 28. 16(1): 1420

TIGAR inhibits glucose-metabolism and cisplatin-chemosensitivity in human lung cancer cells.

Yang Feng, Yiling Meng, Meichao Zhang, Yingxia Ying, Yuan Yao, Dong Li.

TIGAR is an important factor associated with tumor glucose metabolism, but its function and underlying mechanism in human lung cancer remains unclear. Here, we analyzed the expression changes, prognosis, genetic alteration, related gene networks and metabolic pathways of TIGAR in lung cancer. The findings revealed that TIAGR level was augmented in LUAD and LUSC in comparison to the normal lung tissue. In addition, high TIAGR level was related to poorer outcome of patients with LUAD. Different alterations in TIGAR gene at various sites were observed in both LUAD and LUSC. The GO/KEGG analyses indicated that TIGAR affects the occurrence and progress of lung cancer through multiple metabolic pathways. Further, we established lung cancer cell models with TIGAR knockdown or overexpression to explore its effects on glucose metabolism, apoptosis and chemosensitivity. Our results indicated that TIGAR markedly inhibited glucose metabolism, ROS production, and susceptibility of lung cancer cells to cisplatin. Together, TIGAR plays a cancer-promoting role in lung cancer, which becomes a promising prognostic and therapeutic biomarker.

Keywords: Bioinformatics; Chemosensitivity; Lung cancer; Metabolism; TIGAR

DOI: https://doi.org/10.1007/s12672-025-03274-9

J Immunother Cancer. 2025 Jul 31. pii: e012069. [Epub ahead of print]13(7):

Mitochondrial Pathway Signature (MitoPS) predicts immunotherapy response and reveals NDUFB10 as a key immune regulator in lung adenocarcinoma.

Pengpeng Zhang, Mengzhe Zhang, Jianlan Liu, Zhaokai Zhou, Lianmin Zhang, Peng Luo, Zhenfa Zhang.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Although immune checkpoint inhibitors (ICIs) have brought new treatment options for advanced patients, a considerable proportion still shows limited response. Mitochondrial dysfunction plays a crucial role in tumor development and immune evasion, but its regulatory mechanisms in LUAD immune microenvironment remain unclear.
METHODS: We integrated 149 mitochondria-related pathways (1,136 coding proteins) to develop and validate the Mitochondrial Pathway Signature (MitoPS) using machine learning approaches across seven independent LUAD cohorts (n=1,231). The system was systematically compared with 129 published LUAD prognostic signatures and validated in seven immunotherapy cohorts (n=451). Multiomics analysis, immunofluorescence staining, and experimental validation were performed to investigate its molecular mechanism.
RESULTS: MitoPS demonstrated consistent predictive performance across validation cohorts, with high scores indicating poor prognosis, outperforming 129 existing prognostic models. In immunotherapy cohorts, MitoPS reliably predicted treatment response and prognosis. Immune microenvironment analysis revealed that low MitoPS scores correlated with higher immune cell infiltration and active immune function. Mechanistic studies identified mitochondria-related gene NDUFB10 as a core gene of MitoPS (r=0.38, p<0.05), where its high expression was significantly associated with immune desert phenotype and worse prognosis. Functional experiments confirmed that NDUFB10 knockdown significantly enhanced ICIs therapy and increased GZMB+CD8+T cell infiltration, indicating NDUFB10's crucial role in regulating tumor immune microenvironment and immunotherapy response.
CONCLUSION: The MitoPS scoring system reliably predicts prognosis and immunotherapy response in patients with LUAD, providing a novel reference for clinical decision-making. Furthermore, its core gene NDUFB10 regulates tumor immune microenvironment, offering a potential therapeutic target for improving immunotherapy outcomes.

Keywords: Immunotherapy; Lung Cancer

DOI: https://doi.org/10.1136/jitc-2025-012069

Int J Mol Sci. 2025 Jul 16. pii: 6825. [Epub ahead of print]26(14):

Effect of IL-1β on NSCLC-Derived Small Extracellular Vesicles as Actors in Mediating Cancer Progression and Evading Immune System.

BACKGROUND: Increased IL-1β levels may promote carcinogenesis and metastasis by affecting tumor biology and the tumor microenvironment (TME). In this context, extracellular vesicles (EVs) play a key role in cell-to-cell communication, thus modulating the TME and immune response. Here, we aimed to test whether tumor-derived small EVs (TEVs) isolated from sensitive and osimertinib-resistant (OR) non-small-cell lung cancer (NSCLC) cells may promote EMT via fibronectin binding to α5β1 integrin as well as suppress the immune system and if these effects may be favored by IL-1β.
METHODS: TEVs were isolated from control, OR, and IL-1β-stimulated NSCLC cells. Expressions of fibronectin and PD-L1 were screened in TEVs and the mRNA levels of vimentin and SMAD3 were also assessed in cancer cells after TEV co-culturing. Furthermore, to detect the effect on immune cells, we co-cultured TEVs with lung cancer patients' peripheral blood mononuclear cells (PBMCs).
RESULTS: TEVs were positive for fibronectin and the highest protein levels were found in TEVs obtained from the OR and IL-1β-stimulated cells. TEV-mediated activation of α5β1 signaling led to the upregulation of vimentin and SMAD3 mRNA in NSCLC cells and stimulated cell migration. EVs also increased PD-1, CTLA-4, FOXP3, TNF-α, IL-12, and INF-γ mRNA in lung cancer patients' immune cells.
CONCLUSIONS: Our findings indicate that TEVs promote EMT in NSCLC cells by the activation of the fibronectin-α5β1 axis. Finally, IL-1β stimulation induces TEV release with biological properties similar to OR TEVs, thus leading to cancer invasion and immune suppression and suggesting that inflammation can promote tumor spreading.

Keywords: EMT; IL-1β; NSCLCs; cancer progression; immune suppression; tumor-derived small extracellular vesicles (TEVs)

DOI: https://doi.org/10.3390/ijms26146825