The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

Fejza, Albina; Polano, Maurizio; Camicia, Lucrezia; Poletto, Evelina; Carobolante, Greta; Toffoli, Giuseppe; Mongiat, Maurizio; Andreuzzi, Eva

doi:10.3390/ijms22147511

Cited by 16 publications

(12 citation statements)

References 41 publications

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“…Both are elastin microfiber interface proteins that play an important role in imparting elasticity to tissue and blood vessels ( Colombatti et al, 2000 ). Several studies have shown that EMILIN2 is associated with anti-PD1 therapy in melanoma ( Fejza et al, 2021 ). In gastric cancer, EMILIN2 regulates the proliferation of cancer cells through apoptosis ( Andreuzzi et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

EMILIN2 is associated with prognosis and immunotherapy in clear cell renal cell carcinoma

et al. 2022

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Background: EMILIN2 is a platelet-associated elastin that regulates angiogenesis. It has recently been found to play an essential role in various tumors. Nevertheless, the mechanism of action of EMILIN2 in clear cell renal cell carcinoma (ccRCC) remains unclear.Methods: Samples from 33 cancers were obtained from UCSC Xena and The Cancer Genome Atlas (TCGA) database. The relationship between EMILIN2 expression and the clinicopathological characteristics and immune infiltration of ccRCC was investigated. Nonnegative matrix factorization (NMF) was used to classify ccRCC patients. A multigene risk prediction model of ccRCC was constructed using LASSO regression and multivariate regression analysis. A nomogram survival probability prediction map and calibration curve were constructed based on clinical information.Results: EMILIN2 is significantly overexpressed in ccRCC, a phenomenon that is associated with poor prognosis. Meanwhile, EMILIN2 expression is closely related to tumor immune infiltration in ccRCC. Patients with clear cell renal cell carcinoma were divided into two subtypes using NMF, with subtype 2 showed poor prognosis. Next, we established a risk score model for ccRCC based on the common differentially expressed genes (DEGs) between subtypes and groups based on EMILIN2 expression. The results indicated poor prognosis in the high-risk group in the training set and were confirmed in the validation set.Conclusion: Our findings suggest that EMILIN2 expression is closely associated with immune infiltration in ccRCC. EMILIN2 expression is negatively correlated with the prognosis of ccRCC patients. Here, we developed a tool that could predict the prognosis of ccRCC patients.

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Section: Introductionmentioning

confidence: 99%

EMILIN2 is associated with prognosis and immunotherapy in clear cell renal cell carcinoma

et al. 2022

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“…There are several studies that highlight the coupled functions of ECM and the immune system against melanoma. For instance, in a recent study, Fejza et al presented that the ECM proteins are found to be associated with the efficacy of the PD-1 treatments [ 97 ]. Interestingly, in our study, the EC proteins were upregulated, mostly in cell adhesion components, in the late progressive phase of the tumor development and linked to the longer survival rate as well as the response to immunotherapy.…”

Section: Resultsmentioning

confidence: 99%

Deep Proteomic Analysis on Biobanked Paraffine-Archived Melanoma with Prognostic/Predictive Biomarker Read-Out

Szadai

Velásquez

Szeitz

et al. 2021

Cancers

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The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin-embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective biobank pilot study, 90 FFPE samples from 77 patients were processed. Protein quantitation was performed by high-resolution mass spectrometry and validated by histopathologic analysis. The global protein expression formed six sample clusters. Proteins such as TRAF6 and ARMC10 were upregulated in clusters with enrichment for shorter survival, and proteins such as AIFI1 were upregulated in clusters with enrichment for longer survival. The cohort’s heterogeneity was addressed by comparing primary and metastasis samples, as well comparing clinical stages. Within immunotherapy and targeted therapy subgroups, the upregulation of the VEGFA-VEGFR2 pathway, RNA splicing, increased activity of immune cells, extracellular matrix, and metabolic pathways were positively associated with patient outcome. To summarize, we were able to (i) link global protein expression profiles to survival, and they proved to be an independent prognostic indicator, as well as (ii) identify proteins that are potential predictors of a patient’s response to immunotherapy and targeted therapy, suggesting new opportunities for precision medicine developments.

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“…Of the 63 DEGs in monocytes, we generated a signature of 12 overexpressed genes exhibiting immunosuppressive functions and/or associated with a poor cancer prognosis: Cd44 [34], Cd83 [35], Emp1 [36], Eif4e [37], Thbs1 [38], Vegfa [39], Emilin2 [40], Tgm2 [41], Ptgs2 [42], Fn1 [43], Crem [44] , Il1rn [45] (Fig. 5F).…”

Section: By Using Upsetplot Representations To Identify Intersection ...mentioning

confidence: 99%

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Beauséjour

Maggiorani

Lê

et al. 2023

Preprint

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Immune checkpoint inhibitors (ICI) invigorate immune cell functions and are effective against many cancer types. However, the potential of ICI may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of αPD-L1-based cancer immunotherapies is compromised by the accumulation of senescent cells in mice previously exposed to sublethal irradiation or injected with doxorubicin. Similarly, we observed that the efficacy of the combination of a αCTLA-4 antibody with radiotherapy is diminished in previously irradiated mice. In both models, resistance to immunotherapy was associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells by the injection of the senolytic drug ABT263, weeks before treatments, restored immune homeostasis within the tumor micro-environment (TME) and increased mice survival in both models. Using single-cell transcriptomic analysis, we observed that the injection of ABT263 reverses the exacerbated immunosuppressive profile of myeloid cells in the TME of previously irradiated mice. These myeloid cells, when purified from established tumors, were responsible for impaired CD8 T cell proliferation in vitro. Our study shows that cancer therapies, by inducing senescence, favor the formation of an immunosuppressive TME, which can alter the efficacy of ICI. The use of senolytic drugs before ICI may constitute an interesting pharmacological approach to improve the effectiveness of cancer immunotherapies.

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The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

Cited by 16 publications

References 41 publications

EMILIN2 is associated with prognosis and immunotherapy in clear cell renal cell carcinoma

EMILIN2 is associated with prognosis and immunotherapy in clear cell renal cell carcinoma

Deep Proteomic Analysis on Biobanked Paraffine-Archived Melanoma with Prognostic/Predictive Biomarker Read-Out

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

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