Harnessing the immune system for the treatment of melanoma: current status and future prospects

Guennoun, Andrea; Sidahmed, Heba; Maccalli, Cristina; Seliger, Barbara; Marincola, Francesco M.; Bedognetti, Davide

doi:10.1080/1744666x.2016.1176529

Cited by 8 publications

(6 citation statements)

References 132 publications

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“…3 Although a variety of treatment strategies (such as targeted therapies, immune-based approaches, and chemoprevention) have been applied to melanomas, the prognosis of patients with advanced melanoma is still far from being satised. 4,5 For searching more effective treatment options to prevent melanoma developing, the better understanding of the molecular mechanism underlying melanoma progression is imperative.…”

Section: Introductionmentioning

confidence: 99%

SNHG5 promotes proliferation and induces apoptosis in melanoma by sponging miR-155

Liu

Wang

et al. 2018

RSC Adv.

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Section: Introductionmentioning

confidence: 99%

SNHG5 promotes proliferation and induces apoptosis in melanoma by sponging miR-155

Liu

Wang

et al. 2018

RSC Adv.

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“…11,12 The clinical activity of immune checkpoints agents has been conclusively demonstrated for different types of tumors. [13][14][15][16][17][18] The combination treatment with anti-CTLA-4 and anti-PD-1 mAbs for metastatic melanoma yielded striking clinical results, leading to the FDA approval. 19,20 The efficacy of this combination is also under evaluation in other solid tumors such as lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Soluble NKG2D ligands are biomarkers associated with the clinical outcome to immune checkpoint blockade therapy of metastatic melanoma patients

Maccalli

Giannarelli²,

Chiarucci

et al. 2017

OncoImmunology

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The introduction of immune checkpoint blockade into the clinical practice resulted in improvement of survival of a significant portion of melanoma patients. Consequently, predictive biomarkers of response are needed to optimize patient's stratification and the development of combination therapies. The aim of this study was to determine whether levels of soluble NKG2D ligands (MICA, MICB, ULBP1, 2 and 3; sNKG2DLs) in the serum of melanoma patients can serve as useful predictors of response to the treatment with immune checkpoint blockade. sNKG2DLs were measured by ELISA in baseline and post-treatment serum and these results were correlated with the clinical outcome of melanoma patients ( = 194). The same determinations were performed also in a cohort of patients ( = 65) treated with either chemotherapy, radiotherapy, or mutated BRAF inhibitors (BRAFi). Absence of soluble MICB and ULBP-1 in baseline serum correlated with improved survival (OS = 21.6 and 25.3 mo and = 0.02 and 0.01, respectively) of patients treated with immunological therapies while detectable levels of these molecules were found in poor survivors (OS = 8.8 and 12.1 mo, respectively). Multivariate analysis showed that LDH ( <0.0001), sULBP-1 ( = 0.02), and sULBP-2 ( = 0.02) were independent predictors of clinical outcome for the cohort of melanoma patients treated with immune checkpoint blockade. Only LDH but not sNKG2DLs was significantly associated with the clinical outcome of patients treated with standard or BRAFi regimens. These findings highlight the relevance of sNKG2DLs in the serum of melanoma patients as biomarkers for patients' stratification and optimization of immune checkpoint inhibition regimens.

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“…53 Furthermore, the expression of HLA-I molecules and APM components is directly correlated with an improved overall and progression-free survival of melanoma patients in several TCGA datasets. 39,54,55 A reduced mRNA and/or protein expression of various APM components was identified in a large series of melanoma cell lines and lesions, which could be correlated with an increased tumor grading 17,56 implying a deregulated APM component and HLA-I molecule expression. During the last years, some miRs have been reported to target APM components and HLA-I molecules suggesting an important role for post-transcriptional control in the antigen processing and presentation process.…”

Section: Discussionmentioning

confidence: 99%

Identification of miR-200a-5p targeting the peptide transporter TAP1 and its association with the clinical outcome of melanoma patients

et al. 2020

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Tumor escape is often associated with abnormalities in the surface expression of the human leukocyte antigen class I (HLA-I) antigens thereby limiting CD8 + cytotoxic T cell responses. This impaired HLA-I surface expression can be mediated by deficient expression of components of the antigen processing and presentation machinery (APM) due to epigenetic, transcriptional and/or post-transcriptional processes. Since a discordant mRNA and protein expression pattern of APM components including the peptide transporter associated with antigen processing 1 (TAP1) has been frequently described in tumors of distinct origin, a post-transcriptional control of APM components caused by microRNAs (miR) was suggested. Using an in silico approach, miR-200a-5p has been identified as a candidate miR binding to the 3ʹ untranslated region (UTR) of TAP1. Luciferase reporter assays demonstrated a specific binding of miR-200a-5p to the TAP1 3ʹ-UTR. Furthermore, the miR-200a-5p expression is inversely correlated with the TAP1 protein expression in HEK293T cells and in a panel of melanoma cell lines as well as in primary melanoma lesions. High levels of miR-200a-5p expression were associated with a shorter overall survival of melanoma patients. Overexpression of miR-200a-5p reduced TAP1 levels, which was accompanied by a decreased HLA-I surface expression and an enhanced NK cell sensitivity of melanoma cells. These data show for the first time a miRmediated control of the peptide transporter subunit TAP1 in melanoma thereby leading to a reduced HLA-I surface expression accompanied by an altered immune recognition and reduced patients' survival.

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Harnessing the immune system for the treatment of melanoma: current status and future prospects

Cited by 8 publications

References 132 publications

SNHG5 promotes proliferation and induces apoptosis in melanoma by sponging miR-155

SNHG5 promotes proliferation and induces apoptosis in melanoma by sponging miR-155

Soluble NKG2D ligands are biomarkers associated with the clinical outcome to immune checkpoint blockade therapy of metastatic melanoma patients

Identification of miR-200a-5p targeting the peptide transporter TAP1 and its association with the clinical outcome of melanoma patients

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