p75NTR/proBDNF Modulates Basal Cell Carcinoma (BCC) Immune Microenvironment via Necroptosis Signaling Pathway

Lu, Qingli; Qu, Yuanyuan; Yuan, Ding; Kang, Xiaojing

doi:10.1155/2021/6652846

Cited by 6 publications

(5 citation statements)

References 31 publications

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“…Our results support the observations of McDermott et al (2018) and Thompson et al (2007) , showing associations between high immune cell infiltration and poor prognosis. The finding by Lu et al (2021) that p75NTR/proBDNF modulates the immune microenvironment via necroptosis further confirms the close connection between necroptosis and immunity. This implicates both necroptosis and the tumor microenvironment in the prediction of LIHC prognosis.…”

Section: Discussionsupporting

confidence: 62%

Construction and Validation of a Necroptosis-Related Signature Associated With the Immune Microenvironment in Liver Hepatocellular Carcinoma

Wang

Ding

Sun³

et al. 2022

Front. Genet.

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Background: Liver hepatocellular carcinoma (LIHC) is a widespread and often deadly neoplasm. There is increasing evidence that necroptosis mediates numerous tumor-associated behaviors, as well as the regulation of the tumor microenvironment, suggesting its use as a biomarker for tumor prognosis.Methods: Data on mRNA expression and necroptosis regulators were acquired from the TCGA and KEGG databases, respectively. Clinical liver hepatocellular carcinoma (LIHC) patient data and information on the expression of necroptosis regulators were processed by unsupervised cluster analysis was performed on LIHC patients together with necroptotic regulator expression and, differentially expressed necroptosis-related genes (DENRGs) were identified by comparing the two clusters. A signature based on eight DENRGs was constructed and verified through independent data sets, and its relationship with the tumor microenvironment was investigated.Results: Unsupervised cluster analysis demonstrated inherent immune differences among LIHC patients. In all, 1,516 DENRGs were obtained by comparison between the two clusters. In the training set, the final eight genes obtained by univariate, LASSO, and multivariate Cox regression were utilized for constructing the signature. The survival and receiver operating characteristic (ROC) curve achieved satisfactory results in both sets. The high-risk group was characterized by greater immune infiltration and poor prognosis. The results of survival analysis based on the expression of eight DENRGs further confirmed the signature.Conclusion: We established and validated a risk signature based on eight DERNGs related to the tumor microenvironment. This provides a possible explanation for the different clinical effects of immunotherapy and provides a novel perspective for predicting tumor prognosis in LIHC.

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Section: Discussionsupporting

confidence: 62%

Construction and Validation of a Necroptosis-Related Signature Associated With the Immune Microenvironment in Liver Hepatocellular Carcinoma

Wang

Ding

Sun³

et al. 2022

Front. Genet.

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“…Research into TME therapeutic targets is ongoing. Lu et al discovered that the overexpression of the brain-derived neurotrophic factor (BDNF) and its p75 pan-neurotrophin receptor could induce BCC tumor cell death by stimulating M1 macrophages and T cell recruitment on a mouse model, providing a potential therapeutic intervention for Shh inhibitor-resistant tumors [63]. Moreover, by studying cancers with similar TME profiles to that of BCC, researchers have begun investigating the use of therapies for other cancers, such as kidney chromophobe cancers or myxofibrosarcoma, in treating advanced BCC.…”

Section: Therapeutic Considerations For Skin Cancermentioning

confidence: 99%

Review of the Tumor Microenvironment in Basal and Squamous Cell Carcinoma

Chiang

Stafford

Buell

et al. 2023

Cancers

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It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively. However, further investigation of the TME will provide the opportunity to discover novel treatment options.

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“…Nevertheless, the role of CD271 in cSCC remains to be defined. CD271/proBDNF signaling mediates apoptosis in basal cell carcinoma [ 61 ], thus possibly preventing cancer proliferation and development. On the other hand, CD271 has been proposed as a marker of tumor-initiating-cells in oral human and murine SCC cells, and CD271 activation by NGF results in a more invasive phenotype [ 62 ], most likely involving Trk-CD271 heterodimer signaling.…”

Section: Discussionmentioning

confidence: 99%

CD271 activation prevents low to high-risk progression of cutaneous squamous cell carcinoma and improves therapy outcomes

Quadri

Tiso

Musmeci³

et al. 2023

J Exp Clin Cancer Res

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Background Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, showing a rapid increasing incidence worldwide. Although most cSCC can be cured by surgery, a sizeable number of cases are diagnosed at advanced stages, with local invasion and distant metastatic lesions. In the skin, neurotrophins (NTs) and their receptors (CD271 and Trk) form a complex network regulating epidermal homeostasis. Recently, several works suggested a significant implication of NT receptors in cancer. However, CD271 functions in epithelial tumors are controversial and its precise role in cSCC is still to be defined. Methods Spheroids from cSCC patients with low-risk (In situ or Well-Differentiated cSCC) or high-risk tumors (Moderately/Poorly Differentiated cSCC), were established to explore histological features, proliferation, invasion abilities, and molecular pathways modulated in response to CD271 overexpression or activation in vitro. The effect of CD271 activities on the response to therapeutics was also investigated. The impact on the metastatic process and inflammation was explored in vivo and in vitro, by using zebrafish xenograft and 2D/3D models. Results Our data proved that CD271 is upregulated in Well-Differentiated tumors as compared to the more aggressive Moderately/Poorly Differentiated cSCC, both in vivo and in vitro. We demonstrated that CD271 activities reduce proliferation and malignancy marker expression in patient-derived cSCC spheroids at each tumor grade, by increasing neoplastic cell differentiation. CD271 overexpression significantly increases cSCC spheroid mass density, while it reduces their weight and diameter, and promotes a major fold-enrichment in differentiation and keratinization genes. Moreover, both CD271 overexpression and activation decrease cSCC cell invasiveness in vitro. A significant inhibition of the metastatic process by CD271 was observed in a newly established zebrafish cSCC model. We found that the recruitment of leucocytes by CD271-overexpressing cells directly correlates with tumor killing and this finding was further highlighted by monocyte infiltration in a THP-1-SCC13 3D model. Finally, CD271 activity synergizes with Trk receptor inhibition, by reducing spheroid viability, and significantly improves the outcome of photodynamic therapy (PTD) or chemotherapy in spheroids and zebrafish. Conclusion Our study provides evidence that CD271 could prevent the switch between low to high-risk cSCC tumors. Because CD271 contributes to maintaining active differentiative paths and favors the response to therapies, it might be a promising target for future pharmaceutical development.

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p75NTR/proBDNF Modulates Basal Cell Carcinoma (BCC) Immune Microenvironment via Necroptosis Signaling Pathway

Cited by 6 publications

References 31 publications

Construction and Validation of a Necroptosis-Related Signature Associated With the Immune Microenvironment in Liver Hepatocellular Carcinoma

Construction and Validation of a Necroptosis-Related Signature Associated With the Immune Microenvironment in Liver Hepatocellular Carcinoma

Review of the Tumor Microenvironment in Basal and Squamous Cell Carcinoma

CD271 activation prevents low to high-risk progression of cutaneous squamous cell carcinoma and improves therapy outcomes

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