NICE guidance on ipilimumab for treating previously untreated advanced (unresectable or metastatic) melanoma

Hall, Caroline J; Doss, Sally; Robertson, Janet; Adam, Jane

doi:10.1016/s1470-2045(14)70341-9

Cited by 6 publications

(5 citation statements)

References 2 publications

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“…DNA methylation is a prevalent epigenetic pathway and exists in all tumor types. patients, from a value perspective, the optimal sequence and/ or combination of immunotherapies are still unknown (25,26).…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatics analysis of prognostic value and immune cell infiltration of SERPINA1 gene in cutaneous melanoma

Hu¹,

Mei²,

Zhang³

et al. 2022

Ann Transl Med

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Background: Cutaneous melanoma (CM) has a poor overall prognosis. Immune checkpoint inhibitor (ICI) therapy effectively improves overall survival in individuals with advanced melanoma, but only some patients benefit. Serpin Family A Member 1 (SERPINA1), a type of proteinase inhibitor that is used for many targets, is abnormally expressed and plays a vital role in multiple cancers. However, little is known about the clinical significance of SERPINA1 in CM. Methods:The Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) datasets were used to compare SERPINA1 expression levels. The association between SERPINA1 and other clinical factors were examined with R software, and receiver operating characteristic (ROC) curves for identification was developed. The Tumor IMmune Estimation Resource (TIMER) was used to examine the invasion of immune cells, markers for immune cells, and immunological checkpoints. The predictive value of SERPINA1 DNA methylation levels for every CpG was analyzed with the MethSurv web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the roles of genes that interacted with SERPINA1. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict SERPINA1's response to ICIs.Results: SERPINA1 was substantially expressed in CM. Overexpression of SERPINA1 was significantly associated with CM severity. The outcome for individuals with elevated SERPINA1 expression was good (HR =0.54, P<0.001). Using SERPINA1 expression levels, tumors and normal tissues could be reliably differentiated [area under the curve (AUC) =0.889]. Positive associations were found between SERPINA1 in CM and the infiltration of immune cells and immunological checkpoints [programmed cell death-1 (PD-1) and CTLA-4]. The efficacy of immune checkpoint blockade (ICB) in patients with a low expression of SERPINA1 was good. The GO pathway enrichment analysis showed that activation of neutrophil granulocytes participated in enrichment in the immune response pathway. Patients with low SERPINA1 expression had low TIDE scores.Conclusions: SERPINA1 is involved not only in the development and progression of CM but also in the immunological control of CM. Thus, SERPINA1 may serve as a possible biomarker for CM diagnosis, as well as its therapeutic target.

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Section: Discussionmentioning

confidence: 99%

“…Although immunotherapy improves the prognosis of CM patients, from a value perspective, the optimal sequence and/or combination of immunotherapies are still unknown ( 25 , 26 ). Our study indicated that SERPINA1 in CM was positively correlated with many immune cells and checkpoints.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of prognostic value and immune cell infiltration of SERPINA1 gene in cutaneous melanoma

Hu¹,

Mei²,

Zhang³

et al. 2022

Ann Transl Med

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“…Health technology assessments for FDA-approved molecular immunotherapies calculated approx. 80,000 euro per quality-adjusted-life-year [ 35 – 39 ]. To this, the costs of managing immune-related adverse effect should be added; approx.…”

Section: Current Issues In Anti-cancer Immunotherapymentioning

confidence: 99%

The Potential of In Vivo Imaging for Optimization of Molecular and Cellular Anti-cancer Immunotherapies

et al. 2018

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This review aims to emphasize the potential of in vivo imaging to optimize current and upcoming anti-cancer immunotherapies: spanning from preclinical to clinical applications. Immunotherapies are an emerging class of treatments for a variety of diseases. The agents include molecular and cellular therapeutics, which aim to treat the disease through re-education of the host immune system, often via complex mechanisms of action. In vivo imaging has the potential to contribute in several different ways: (1) as a drug development tool to improve our understanding of their complex mechanisms of action, (2) as a tool to predict efficacy, for example, to stratify patients into probable responders and likely non-responders, and (3) as a non-invasive treatment response biomarker to guide efficient immunotherapy use and to recognize early signs of potential loss of efficacy or resistance in patients. Areas where in vivo imaging is already successfully implemented in onco-immunology research will be discussed and domains where its use offers great potential will be highlighted. The focus of this article is on anti-cancer immunotherapy as it currently is the most advanced immunotherapy area. However, the described concepts can also be paralleled in other immune-mediated disorders and for conditions requiring immunotherapeutic intervention. Importantly, we introduce a new study group within the European Society of Molecular Imaging with the goal to facilitate and enhance immunotherapy development through the use of in vivo imaging.

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“…CTLA-4 maintains peripheral tolerance by enhancing regulatory T cell (Treg) functions; thus, undirected control of the effector T cells ( 6 ) and overexpression of CTLA-4 in tumor samples implicates poor prognosis in patients with melanoma ( 7 ). Because CTLA-4 inhibition results in increased activation of the immune system, Ipilimumab, an inhibitor of CTLA-4, was approved for the treatment of advanced or unresectable melanoma ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

CTLA-4 Synergizes With PD1/PD-L1 in the Inhibitory Tumor Microenvironment of Intrahepatic Cholangiocarcinoma

Guo

Zeng

et al. 2021

Front. Immunol.

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Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed. Deciphering CTLA-4 and PD-L1 interactions in ICC enable targeted therapy for this disease. In this study, immunohistochemistry (IHC) was used to detect and quantify CTLA-4, forkhead box protein P3 (FOXP3), and PD-L1 in samples from 290 patients with ICC. The prognostic capabilities of CTLA-4, FOXP3, and PD-L1 expression in ICC were investigated with the Kaplan–Meier method. Independent risk factors related to ICC survival and recurrence were assessed by the Cox proportional hazards models. Here, we identified that CTLA-4+ lymphocyte density was elevated in ICC tumors compared with peritumoral hepatic tissues (P <.001), and patients with a high density of CTLA-4+ tumor-infiltrating lymphocytes (TILsCTLA-4 High) showed a reduced overall survival (OS) rate and increased cumulative recurrence rate compared with patients with TILsCTLA-4 Low (P <.001 and P = .024, respectively). Similarly, patients with high FOXP3+ TILs (TILsFOXP3 High) had poorer prognoses than patients with low FOXP3+ TILs (P = .021, P = .034, respectively), and the density of CTLA-4+ TILs was positively correlated with FOXP3+ TILs (Pearson r = .31, P <.001). Furthermore, patients with high PD-L1 expression in tumors (TumorPD-L1 High) and/or TILsCTLA-4 High presented worse OS and a higher recurrence rate than patients with TILsCTLA-4 LowTumorPD-L1 Low. Moreover, multiple tumors, lymph node metastasis, and high TumorPD-L1/TILsCTLA-4 were independent risk factors of cumulative recurrence and OS for patients after ICC tumor resection. Furthermore, among ICC patients, those with hepatolithiasis had a higher expression of CTLA-4 and worse OS compared with patients with HBV infection or undefined risk factors (P = .018). In conclusion, CTLA-4 is increased in TILs in ICC and has an expression profile distinct from PD1/PD-L1. TumorPD-L1/TILsCTLA-4 is a predictive factor of OS and ICC recurrence, suggesting that combined therapy targeting PD1/PD-L1 and CTLA-4 may be useful in treating patients with ICC.

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NICE guidance on ipilimumab for treating previously untreated advanced (unresectable or metastatic) melanoma

Cited by 6 publications

References 2 publications

Bioinformatics analysis of prognostic value and immune cell infiltration of SERPINA1 gene in cutaneous melanoma

Bioinformatics analysis of prognostic value and immune cell infiltration of SERPINA1 gene in cutaneous melanoma

The Potential of In Vivo Imaging for Optimization of Molecular and Cellular Anti-cancer Immunotherapies

CTLA-4 Synergizes With PD1/PD-L1 in the Inhibitory Tumor Microenvironment of Intrahepatic Cholangiocarcinoma

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