The Apelin/APLNR system modulates tumor immune response by reshaping the tumor microenvironment

Yang, Yuqin; Chen, Meilin; Qiu, Yanbing; Li, Xiaoxu; Huang, Yumei; Zhang, Wenling

doi:10.1016/j.gene.2022.146564

Cited by 9 publications

(5 citation statements)

References 109 publications

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“…We also observed that patients whose NLR increases during ICIs treatment have poor survival compared to patients whose NLR is unchanged, and we found that a high NLR pos t/NLR baseline is correlated with APNLR and WNT5A. The Apelin/APLNR system is increased in some cancers, is involved in tumor microenvironment reshaping and modulates tumor immune response [ 28 ].…”

Section: Discussionmentioning

confidence: 85%

CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy

Mallardo,

Fordellone,

White

et al. 2023

J Transl Med

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Background Identifying response markers is highly needed to guide the treatment strategy in patients with metastatic melanoma. Methods A retrospective study was carried out in patients with unresectable/metastatic melanoma (stage IIIb–IV), treated with anti-PD-1 in the first line setting, to better explore the role and the timing of neutrophil/lymphocyte ratio (NLR) as potential biomarker of response. The relationship of NLR with inflammation-immune mediators and the underlying negative effect of raising NLR during immunotherapy, have been investigated with transcriptomic gene analysis. Results The results confirmed previous findings that a high baseline NLR is associated with a poorer prognosis and with higher serum level of lactate dehydrogenase (LDH), regardless of the presence of brain metastases. The transcriptomic analysis showed that high baseline NLR is associated with a characteristic gene signature CCNA1, LDHA and IL18R1, which correlates with inflammation and tumorigenesis. Conversely, low baseline NLR is associated with the signature CD3, SH2D1A, ZAP70 and CD45RA, linked to the immune-activation. The genes positively associated with NLR (CD39 (ENTPD1), PTEN, MYD88, MMP9 and LDH) are involved in processes of immunosuppression, inflammation and tumor-promoting activity. Increased expression of CD39 correlated with TGFβ2, a marker of the N2 neutrophils with immunosuppressive activity. Conclusions These results suggest that increasing NLR is associated with an increased neutrophil population, with polarization to the N2 phenotype, and this process may be the basis for the negatively prognostic role of NLR.

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Section: Discussionmentioning

confidence: 85%

CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy

Mallardo,

Fordellone,

White

et al. 2023

J Transl Med

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“…The APLNR gene, namely APJ, is situated on chromosome 11q12 and stands out as an intriguing member of the G protein-coupled receptor family, classified as an orphan receptor in group A. 28 As the ligand for the APJ receptor, Apelin was originally isolated from bovine stomach extracts. 29 The Apelin/APJ system is diffusely distributed throughout the human body, with a particularly robust presence on endothelial cells (ECs).…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA-Sequencing Analyses Identify APLNR, INS-IGF2, RGCC Genes May Be Involved in the Pathogenesis of Systemic Sclerosis Skin

Zhu,

Deng

2024

CCID

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Background Systemic sclerosis represents a persistent autoimmune disorder marked with fibrosis affecting both skin and other organs, which leads to a diminished quality of life and increased mortality. The affected skin provides a valuable opportunity to explore the pathogenesis of systemic sclerosis. Nevertheless, the roles of various cell populations within scleroderma remain intricate. Methods We conducted a comprehensive reanalysis of recently published single-cell RNA-sequencing data from skin tissue cells in scleroderma. Through the utilization of Seurat, irGSEA, AUCell packages, and WGCNA analysis, we aimed to unveil crucial genes associated with the disease’s etiological factors. Our investigation involved the characterization of heterogeneous pathway activities in both healthy and SSc-affected skin. Furthermore, we employed immunofluorescence techniques to validate the expression patterns of hub genes and differentially expressed genes. Results The Endothelial-to-Mesenchymal Transition (EndMT) pathway was upregulated in SSc skin. Notably, the M4 module within Endothelial cell subpopulation 1 exhibited a strong association with EndMT. Furthermore, we identified three overexpressed genes ( APLNR , I NS-IGF2, RGCC ) that demonstrated a significant correlation with EndMT. Importantly, their expression levels were markedly higher in skin of individuals with SSc when compared to healthy controls. Conclusion APLNR, INS-IGF2 and RGCC serve as potential key players in the pathogenesis of SSc skin through EndMT-dependent mechanisms.

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“…A ligand-activated helix-loop-helix transcription factor known as AHR -encoded proteins is implicated in the modulation of physiological reactions to planar aromatic hydrocarbons 35 , 36 . APLNR encodes a member of the gene family for G protein-coupled receptors, which, although linked to the angiotensin receptor, is actually an apelin receptor that inhibits adenylate cyclase activity and reverses the stress effects of angiotensin II (Ang II) by causing a hypertensive response 37 , 38 . ITGA10 encodes an integrin alpha chain and is highly expressed in chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Predicting feature genes correlated with immune infiltration in patients with abdominal aortic aneurysm based on machine learning algorithms

Zhang,

2024

Sci Rep

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Abdominal aortic aneurysm (AAA) is a condition characterized by a pathological and progressive dilatation of the infrarenal abdominal aorta. The exploration of AAA feature genes is crucial for enhancing the prognosis of AAA patients. Microarray datasets of AAA were downloaded from the Gene Expression Omnibus database. A total of 43 upregulated differentially expressed genes (DEGs) and 32 downregulated DEGs were obtained. Function, pathway, disease, and gene set enrichment analyses were performed, in which enrichments were related to inflammation and immune response. AHR, APLNR, ITGA10 and NR2F6 were defined as feature genes via machine learning algorithms and a validation cohort, which indicated high diagnostic abilities by the receiver operating characteristic curves. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was used to quantify the proportions of immune infiltration in samples of AAA and normal tissues. We have predicted AHR, APLNR, ITGA10 and NR2F6 as feature genes of AAA. CD8 + T cells and M2 macrophages correlated with these genes may be involved in the development of AAA, which have the potential to be developed as risk predictors and immune interventions.

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The Apelin/APLNR system modulates tumor immune response by reshaping the tumor microenvironment

Cited by 9 publications

References 109 publications

CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy

CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy

Single-Cell RNA-Sequencing Analyses Identify APLNR, INS-IGF2, RGCC Genes May Be Involved in the Pathogenesis of Systemic Sclerosis Skin

Predicting feature genes correlated with immune infiltration in patients with abdominal aortic aneurysm based on machine learning algorithms

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