Obesity accelerates immune evasion of non-small cell lung carcinoma via TFEB-dependent upregulation of Siglec-15 and glycolytic reprogramming

Zhang, Cai; Zhou, Lijie; Li, Songyang; Zhao, Junwei; Meng, Xianchun; Ma, Liwei; Wang, Yongfeng; Li, Cai; Ming, Liang

doi:10.1016/j.canlet.2022.215918

Cited by 10 publications

(5 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 As for underlying mechanism, Zhang et al revealed that obesity could accelerate immune evasion of non-small cell lung carcinoma via TFEB-dependent up-regulation of Siglec-15 and glycolytic reprogramming. 26 In this present study, we collected tissue samples to perform qPCR, western blotting, and IHC analyses to further investigate Siglec-15 expression in LUAD. The qPCR test with 16 LUAD samples showed substantially elevated expression of Siglec-15 in cancer tissues than that in noncancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Li et al stated that patients with low CD8A expression/CD8 + T cells infiltration and high Siglec‐15 expression were related to the activation of immunosuppressive signature and metabolism‐related pathway, along with increased infiltration of TAMs 23 . As for underlying mechanism, Zhang et al revealed that obesity could accelerate immune evasion of non‐small cell lung carcinoma via TFEB‐dependent up‐regulation of Siglec‐15 and glycolytic reprogramming 26 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The expression characteristic and prognostic role of Siglec‐15 in lung adenocarcinoma

Sun,

Du,

et al. 2024

Clinical Respiratory J

View full text Add to dashboard Cite

Sialic acid‐binding immunoglobulin‐like lectin‐15 (Siglec‐15) has been identified as an immune suppressor and a promising candidate for immunotherapy of cancer management. However, the association between Siglec‐15 expression and clinicopathological features of lung adenocarcinoma (LUAD), especially the prognostic role, is not fully elucidated. In this present study, a serial of bioinformatics analyses in both tissue and cell levels were conducted to provide an overview of Siglec‐15 expression. Real‐time quantitative PCR (qPCR) test, western blotting assay, and immunohistochemistry (IHC) analyses were conducted to evaluate the expression of Siglec‐15 in LUAD. Survival analysis and Kaplan–Meier curve were employed to describe the prognostic parameters of LUAD. The results of bioinformatics analyses demonstrated the up‐regulation of Siglec‐15 expression in LUAD. The data of qPCR, western blotting, and IHC analyses further proved that the expression of Siglec‐15 in LUAD tissues was significantly increased than that in noncancerous tissues. Moreover, the expression level of Siglec‐15 protein in LUAD was substantially associated with TNM stage. LUAD cases with up‐regulated Siglec‐15 expression, positive N status, and advance TNM stage suffered a critical unfavorable prognosis. In conclusion, Siglec‐15 could be identified as a novel prognostic biomarker in LUAD and targeting Siglec‐15 may provide a promising strategy for LUAD immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The expression characteristic and prognostic role of Siglec‐15 in lung adenocarcinoma

Sun,

Du,

et al. 2024

Clinical Respiratory J

View full text Add to dashboard Cite

show abstract

“…Meanwhile, obesity and diabetes are risk factors for gastrointestinal tumors. Of note, a recent study has demonstrated that obesity can accelerate immune evasion of non-small cell lung carcinoma via upregulation of immune checkpoint Siglec-15 and glycolytic reprogramming [30].…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine demethylase FTO serves as an indicator for predicting prognosis and immunotherapy response in individuals with gastric cancer

Jia¹,

Zhou²,

Li³

et al. 2023

Preprint

View full text Add to dashboard Cite

The predictive abilities of m6A regulators for the prognosis and immunotherapy response in gastric cancer (GC) remain indistinct. FTO was overexpressed and predicted poor prognosis in GC. Based on consensus clustering analysis, two independent subgroups (G1/G2) were identified. Notably, FTO was upregulated in the G1 subgroup. Meanwhile, the infiltration level of CD8+ T cells was strikingly decreased while the stemness features were enhanced in the G1 subgroup. More importantly, FTO was negatively correlated with MSI and TMB. Furthermore, ICB response prediction indicated that patients with upregulated FTO showed high TIDE scores. Subsequently, FTO was confirmed to be related to multiple immune checkpoints, particularly PD-L1. Specifically, FTO was dramatically upregulated in GC cell lines and clinical cancer samples. Functional experiments illustrated that FTO acted as an oncogene to facilitate malignant phenotypes. Notably, PD-L1 was remarkably downregulated after RNA interference-mediated knockdown of FTO.FTO can aggravate GC malignant phenotypes. More importantly, it could be utilized to predict the long-term prognosis and the immunotherapy response in GC individuals. However, larger trials should be performed to verify the prediction accuracy.

show abstract

“…Transcription factor EB (TFEB) gene can upregulate Siglec-15 expression, then bind to Ldha and Hk2 promoters thereby enhancing glycolytic influx in NSCLC cells. Inhibiting TFEB is found to improve the anti-PD-1 therapeutic efficiency in obese mice; thus, TFEB is a biomarker in predicting immune checkpoint blockade [ 58 ].…”

Section: Metabolic Reprogramming In Nsclcmentioning

confidence: 99%

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

Bajinka,

Ouedraogo,

Golubnitschaja

et al. 2024

EPMA Journal

View full text Add to dashboard Cite

Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease).The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches.Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles—all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subpopulations, affected patients, and healthcare at large.

show abstract

Obesity accelerates immune evasion of non-small cell lung carcinoma via TFEB-dependent upregulation of Siglec-15 and glycolytic reprogramming

Cited by 10 publications

References 48 publications

The expression characteristic and prognostic role of Siglec‐15 in lung adenocarcinoma

The expression characteristic and prognostic role of Siglec‐15 in lung adenocarcinoma

N6-methyladenosine demethylase FTO serves as an indicator for predicting prognosis and immunotherapy response in individuals with gastric cancer

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

Contact Info

Product

Resources

About