Immune cells in the melanoma microenvironment hold information for prediction of the risk of recurrence and response to treatment

Camisaschi, Chiara; Vallacchi, Viviana; Castelli, Chiara; Rivoltini, Licia; Rodolfo, Monica

doi:10.1586/14737159.2014.928206

Cited by 24 publications

(17 citation statements)

References 19 publications

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“…The tumor microenvironment (TME) involves infiltration of multiple immune cell subsets, and the pattern of immune cell infiltration (ICI) could influence the prognosis and clinical benefit of melanoma immune therapy (8,9). TME is a vital factor that determines the efficacy of anti-tumor immune therapy (10).…”

Section: Introductionmentioning

confidence: 99%

Tumor Immune Microenvironment Characterization Identifies Prognosis and Immunotherapy-Related Gene Signatures in Melanoma

Liú

Yang

2021

Front. Immunol.

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BackgroundThe tumor microenvironment (TME) involves infiltration of multiple immune cell subsets, which could influence the prognosis and clinical characteristics. The increasing evidence on the role of tumor-infiltrating lymphocytes (TILs) in primary and metastatic melanomas supports that the immune system is involved in the progression and outcomes of melanoma. However, the immune infiltration landscape in melanoma has not been systematically elucidated.MethodsIn this study, we used CIBERSORT and ESTIMATE algorithms to analyze immune infiltration pattern of 993 melanoma samples. Then we screened differential expression genes (DEGs) related to immune subtypes and survival. The immune cell infiltration (ICI) score was constructed by using principal-component analysis (PCA) based on immune signature genes from DGEs. Gene set enrichment analysis (GSEA) was applied to explore high and low ICI score related pathways. Finally, the predictive ability of ICI score was evaluated in survival prognosis and immunotherapy benefit.ResultWe identified three ICI clusters and three gene clusters associated with different immune subtypes and survival outcomes. Then the ICI score was constructed, and we found that high ICI score exhibited activated immune characteristics and better prognosis. High ICI score was significantly enriched in immune pathways and highly expressed immune signature genes. More importantly, we confirmed that melanoma patients with high ICI score had longer overall survival and rate of response to immunotherapy.ConclusionWe presented a comprehensive immune infiltration landscape in melanoma. Our results will facilitate understanding of the melanoma tumor microenvironment and provide a new immune therapy strategy.

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Section: Introductionmentioning

confidence: 99%

Tumor Immune Microenvironment Characterization Identifies Prognosis and Immunotherapy-Related Gene Signatures in Melanoma

Liú

Yang

2021

Front. Immunol.

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“…Although further studies are currently ongoing, until now, immunotherapy has been shown to be an effective and helpful therapeutic option mainly for some tumors considered generally more immunogenic, including non-small-cell lung cancer (NSCLC), melanoma and renal cell carcinoma (RCC) [4–7]. The tumor microenvironment (TME) of these tumors is characterized by the abundant presence of several immune cells, including macrophages and T lymphocytes, which, if adequately activated, release cytokines, interleukins and growth factors [8]. The anti-tumor immune response induction needs three major activation signals that involve (1) the interaction between molecules with co-stimulatory function on antigen-presenting cells (APCs) and receptors present on T lymphocytes; (2) the link between tumor-associated antigens (TAAs) exposed by major histocompatibility complex (MHC) and T-cell receptor (TCR); finally, the production of inflammatory cytokines such as interleukin-12 (IL-12) and type I IFN (IFN alpha/beta) [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC)

et al. 2019

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Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ 50% for first-line therapy and ≥ 1% for second-line treatment, respectively) showed better response rates to immunotherapy and longer survival in first-line therapy compared with conventional chemotherapy. PD-L1, whose expression is evaluated by using immunohistochemistry analysis, is currently the only biomarker approved for clinical use in the first- and second-line monotherapy setting and therefore plays a central role in treatment decision-making for patients with advanced NSCLC. In this review we will discuss the key role of PD-L1 as a predictive biomarker of response to pembrolizumab therapy in NSCLC patients by describing the appropriate techniques and methodologies for immunohistochemical evaluation of PD-L1 expression and providing an overview of the clinical studies supporting its predictive significance.

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“…Melanoma tumors are characterized by high immunogenicity and are typically infiltrated by different types of immune cells (4,5). Previous studies have shown that high level of immune cell infiltration was associated with favorable clinical outcomes of patients in both primary (6–9) and metastatic melanoma (10–14). Jonsson et al defined four molecular subtypes using gene expression data from a cohort of stage IV melanoma patients and further validated them in another cohort consisting of both stage III and IV melanoma patients (15).…”

Section: Introductionmentioning

confidence: 99%

A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis

Zhao

Schaafsma

Gorlov

et al. 2019

Molecular Cancer Research

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Melanoma is the most aggressive type of skin cancer in the United States with an increasing incidence. Melanoma lesions often exhibit high immunogenicity, with infiltrating immune cells playing important roles in regression of tumors occurring spontaneously or caused by therapeutic treatment. Computational and experimental methods have been used to estimate the abundance of immune cells in tumors, but their applications are limited by the requirement of large gene sets or multiple antibodies. Although the prognostic role of immune cells has been appreciated, a systematic investigation of their association with clinical factors, genomic features, prognosis and treatment response in melanoma is still lacking. This study, identifies a 25-gene signature based on RNA-seq data from The Cancer Genome Atlas (TCGA)-Skin Cutaneous Melanoma (TCGA-SKCM) dataset. This signature was used to calculate sample-specific Leukocyte Infiltration Scores (LIS) in six independent melanoma microarray datasets and scores were found to vary substantially between different melanoma lesion sites and molecular subtypes. For metastatic melanoma, LIS was prognostic in all datasets with high LIS being associated with good survival. The current approach provided additional prognostic information over established clinical factors, including age, tumor stage, and gender. In addition, LIS was predictive of patient survival in stage III melanoma, and treatment efficacy of tumor-specific antigen vaccine. This study identifies a 25-gene signature that effectively estimates the level of immune cell infiltration in melanoma, which provides a robust biomarker for predicting patient prognosis.

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Immune cells in the melanoma microenvironment hold information for prediction of the risk of recurrence and response to treatment

Cited by 24 publications

References 19 publications

Tumor Immune Microenvironment Characterization Identifies Prognosis and Immunotherapy-Related Gene Signatures in Melanoma

Tumor Immune Microenvironment Characterization Identifies Prognosis and Immunotherapy-Related Gene Signatures in Melanoma

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC)

A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis

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