Crosstalk between cGAS-STING pathway and autophagy in cancer immunity

Lu, Qijun; Chen, Yukun; Li, Jianwen; Zhu, Feng; Zheng, Zhaoqing

doi:10.3389/fimmu.2023.1139595

Cited by 13 publications

(12 citation statements)

References 171 publications

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“…But which signals are critical for conveying the proinflammatory and antitumor effects of autophagy ablation in TECs? Recent studies have largely focused on the crosstalk between autophagy and STING pathways and their effects on cancer cell immunogenicity/antitumor immunity in response to therapy (Zhao et al , 2022; Lu et al , 2023). However, emerging evidence indicates that the homeostatic and pathological functions of autophagy in ECs are shaped by the cellular and tissue/microenvironment context (Reglero‐Real et al , 2021; Amersfoort et al , 2022; Meçe et al , 2022) and respond to different inflammatory cues.…”

Section: Discussionmentioning

confidence: 99%

Tumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma

Verhoeven,

Jacobs,

Rizzollo

et al. 2023

EMBO Mol Med

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Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune‐excluded tumor phenotype. However, the molecular mechanisms that sustain TEC‐mediated immunosuppression remain largely elusive. Here, we show that autophagy ablation in TECs boosts antitumor immunity by supporting infiltration and effector function of T‐cells, thereby restricting melanoma growth. In melanoma‐bearing mice, loss of TEC autophagy leads to the transcriptional expression of an immunostimulatory/inflammatory TEC phenotype driven by heightened NF‐kB and STING signaling. In line, single‐cell transcriptomic datasets from melanoma patients disclose an enriched InflammatoryHigh/AutophagyLow TEC phenotype in correlation with clinical responses to immunotherapy, and responders exhibit an increased presence of inflamed vessels interfacing with infiltrating CD8+ T‐cells. Mechanistically, STING‐dependent immunity in TECs is not critical for the immunomodulatory effects of autophagy ablation, since NF‐kB‐driven inflammation remains functional in STING/ATG5 double knockout TECs. Hence, our study identifies autophagy as a principal tumor vascular anti‐inflammatory mechanism dampening melanoma antitumor immunity.

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Section: Discussionmentioning

confidence: 99%

Tumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma

Verhoeven,

Jacobs,

Rizzollo

et al. 2023

EMBO Mol Med

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“…From the observation that tumor cells are capable of modulating autophagy to promote their survival and resistance to current clinical treatments (radiotherapy and chemotherapy), studies about autophagy in cancer have expanded dramatically [ 197 , 198 ]. On the basis of these studies, few novel autophagy inhibitors have been identified which have been then tested in human clinical trials.…”

Section: Potential Clinical Application For Adoptive Cell-therapymentioning

confidence: 99%

Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies

Giansanti,

Theinert,

Boeing

et al. 2023

Mol Cancer

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Autophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy. However, very little is known about the role and impact of autophagy in T and NK cells, the main players in the active fight against infections and tumors. Important questions are emerging: what role does autophagy play on T/NK cells? Could its modulation lead to any advantages? Could specific targeting of autophagy on tumor cells (blocking) and T/NK cells (activation) be a new intervention strategy? In this review, we debate preclinical studies that have identified autophagy as a key regulator of immune responses by modulating the functions of different immune cells and discuss the redundancy or diversity among the subpopulations of both T and NK cells in physiologic context and in cancer.

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“…Psoriasis is an autoinflammatory disease that affects not only skin but multiple organs thus being associated with many comorbidities (1). The prevalence of psoriasis differs between the regions, i.e.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and metabolic biomarkers in patients with Psoriasis

Bakić,

Klisić,

Kocić

et al. 2024

J Med Biochemistry

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Background: Psoriasis is an autoinflammatory disease that affects not only skin, but multiple organs thus being associated with many comorbidities. Oxidative stress and inflammation play the major role in the pathogenesis of this disease. Studies that examined by-products of oxidative stress in psoriasis show discrepant results. Hence, we aimed to examine the oxidative stress, inflammation and metabolic markers and to explore their potential relationship with disease severity in patients with psoriasis. Methods: This case-control study comprised of 35 patients with psoriasis and 35 age, sex and body mass index-matched healthy controls. Metabolic and oxidative stress biomarkers [i.e., malondialdehyde (MDA), advanced oxidation protein products (AOPP), and catalase (CAT)] were measured. The principal component analysis (PCA) was employed to reduce the number of measured variables into smaller number of factors. Results: Higher AOPP levels (p<0.01) and CAT activity (p<0.001), but no difference in MDA levels in psoriasis patients vs. healthy controls were shown. Multivariate binary logistic regression analysis showed that a combination of metabolic related factor (i.e., glucose and triglycerides) and renal function related factor (i.e., creatinine and urea) was the best model for Psoriasis Area and Severity Index (PASI) >10 prediction, while oxidative stress-hepatic related factor (i.e., MDA, alanine aminotransferase) was selected as the best predictor for Dermatology Life Quality Index (DLQI) >20. Conclusion: Multimarker approach showed that metabolic and renal function related factor and oxidative stress-hepatic related factor were better predictors of psoriasis severity than each single examined biomarker.

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Crosstalk between cGAS-STING pathway and autophagy in cancer immunity

Cited by 13 publications

References 171 publications

Tumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma

Tumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma

Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies

Oxidative stress and metabolic biomarkers in patients with Psoriasis

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