Advances in Immunotherapy for Melanoma: A Comprehensive Review

Rodríguez-Cerdeira, Carmen; Carnero-Gregorio, Miguel; López-Bárcenas, Adriana; Sánchez-Blanco, Elena; Sánchez-Blanco, B.; Fabbrocini, Gabriella; Bardhi, Brunilda; Sinani, Ardiana; Guzmán, Roberto Arenas

doi:10.1155/2017/3264217

Cited by 101 publications

(85 citation statements)

References 50 publications

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“…75%) affecting specific genes, which lead to an increasing proliferation and survival (Kozar et al, 2019). Immunotherapy is being exploited and investigated, and can be grouped in five types: (i) targeted antibodies (Sanlorenzo et al, 2014;Herzberg and Fisher, 2016); (ii) adoptive cell therapy (Sanlorenzo et al, 2014); (iii) oncolytic virus therapy (Franklin et al, 2017); (iv) cancer vaccines (Tuettenberg et al, 2007;Rodriguez-Cerdeira et al, 2017); and (v) immunomodulators (Johnson et al, 2014;Faries, 2016;Cancer Research Institute, 2019). Chemotherapy and immunotherapy, can be combined (biochemotherapy) regarding the stage disease (Sanlorenzo et al, 2014;Kozar et al, 2019).…”

Section: Melanomamentioning

confidence: 99%

Melanoma in the Eyes of Mechanobiology

Brás

Radmacher

Sousa

et al. 2020

Front. Cell Dev. Biol.

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Skin is the largest organ of the human body with several important functions that can be impaired by injury, genetic or chronic diseases. Among all skin diseases, melanoma is one of the most severe, which can lead to death, due to metastization. Mechanotransduction has a crucial role for motility, invasion, adhesion and metastization processes, since it deals with the response of cells to physical forces. Signaling pathways are important to understand how physical cues produced or mediated by the Extracellular Matrix (ECM), affect healthy and tumor cells. During these processes, several molecules in the nucleus and cytoplasm are activated. Melanocytes, keratinocytes, fibroblasts and the ECM, play a crucial role in melanoma formation. This manuscript will address the synergy among melanocytes, keratinocytes, fibroblasts cells and the ECM considering their mechanical contribution and relevance in this disease. Mechanical properties of melanoma cells can also be influenced by pigmentation, which can be associated with changes in stiffness. Mechanical changes can be related with the adhesion, migration, or invasiveness potential of melanoma cells promoting a high metastization capacity of this cancer. Mechanosensing, mechanotransduction, and mechanoresponse will be highlighted with respect to the motility, invasion, adhesion and metastization in melanoma cancer.

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Section: Melanomamentioning

confidence: 99%

Melanoma in the Eyes of Mechanobiology

Brás

Radmacher

Sousa

et al. 2020

Front. Cell Dev. Biol.

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“…Cancer immunotherapies aim to shift the balance back to dominant antitumor immunity through various approaches, including antibody blockade of immunosuppressive signaling pathways, vaccination, or adoptive transfer of activated or engineered T cells (44). Tumor-associated PD-L1 expression is predictive of clinical response to PD-1-directed immunotherapy.…”

Section: Elevated Mpges1 Expression Is Associated With Low Cd8 þ T-cementioning

confidence: 99%

The COX2 Effector Microsomal PGE2 Synthase 1 is a Regulator of Immunosuppression in Cutaneous Melanoma

Kim

Roszik

Cho

et al. 2019

Clinical Cancer Research

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Purpose: Microsomal prostaglandin E2 synthase 1 (mPGES1) was evaluated as an important downstream effector of the COX2 pathway responsible for tumor-mediated immunosuppression in melanoma.Experimental Design: The analysis of a stage III melanoma tissue microarray (n ¼ 91) was performed to assess the association between mPGES1, COX2, CD8, and patient survival. Pharmacologic inhibitors and syngeneic mouse models using PTGES-knockout (KO) mouse melanoma cell lines were used to evaluate the mPGES1-mediated immunosuppressive function.Results: We observed correlations in expression and colocalization of COX2 and mPGES1, which are associated with increased expression of immunosuppressive markers in human melanoma. In a syngeneic melanoma mouse model, PTGES KO increased melanoma expression of PD-L1, increased infiltration of CD8a þ T cells, and CD8a þ dendritic cells into tumors and suppressed tumor growth. Durable tumor regression was observed in mice bearing PTGES KO tumors that were given anti-PD-1 therapy. Analysis of a stage III melanoma tissue microarray revealed significant associations between high mPGES1 expression and low CD8 þ infiltration, which correlated with a shorter patient survival.Conclusions: Our results are the first to illustrate a potential role for mPGES1 inhibition in melanoma immune evasion and selective targeting in supporting the durability of response to PD-1 checkpoint immunotherapy. More research effort in this drug development space is needed to validate the use of mPGES1 inhibitors as safe treatment options. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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“…1 Hence, combinations of new immunotherapy technologies and immunotherapeutic agents are being studied with a specific focus on exposing tumor antigens in an immunogenic milieu. 1,7 ONCOS-102 (Ad5/3-Δ24-GM-CSF) is an engineered oncolytic adenovirus (Ad5/3) that expresses granulocyte-macrophage colony-stimulating factor (GM-CSF). 8 Its chimeric 5/3 capsid contains the fiber knob derived from Ad serotype 3, so infection can occur through binding of the desmoglein 2 receptor, which is often expressed on tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model

2018

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Malignant melanoma is an aggressive type of skin cancer whose incidence is increasing globally. Although surgery is effective in early stage melanoma, patients with advanced melanoma only have a 20% 5-year survival rate. Hence, combinations of existing and new immunotherapy technologies and immunotherapeutic agents are being evaluated. ONCOS-102 is an oncolytic adenovirus armed with human GM-CSF and an Ad5/3 chimeric capsid. It has shown to be well tolerated in phase I study (NCT01598129) wherein it induced antitumor immunity, infiltration of CD8 + T cells to tumors, and up-regulation of PD-L1. We propose that ONCOS-102 could serve as an immunosensitizer in combination therapies with checkpoint inhibitors. In this preclinical study, we investigated the cytotoxicity of ONCOS-102 and pembrolizumab, an anti-PD-1 antibody, in four human melanoma cell lines, A375, A2058, SK-Mel-2 and SK-Mel-28. Humanized mice engrafted with A2058 melanoma cells showed significant tumor volume reduction after ONCOS-102 treatment. Combination of pembrolizumab with ONCOS-102 reduced tumor volume to an even greater extent, while pembrolizumab (200 µg, or 400 µg) did not show any therapeutic benefit by itself. Body weight loss, and metastasis were not significantly affected by any treatment. These data support the scientific rationale for the ongoing clinical study of combination therapy of ONCOS-102 and pembrolizumab for the treatment of melanoma (NCT03003676).

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Advances in Immunotherapy for Melanoma: A Comprehensive Review

Cited by 101 publications

References 50 publications

Melanoma in the Eyes of Mechanobiology

Melanoma in the Eyes of Mechanobiology

The COX2 Effector Microsomal PGE2 Synthase 1 is a Regulator of Immunosuppression in Cutaneous Melanoma

Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model

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