Macrophages in melanoma: A double‑edged sword and targeted therapy strategies (Review)

Zhou, Qiujun; Fang, Tingting; Wei, Shenyu; Chai, Shiqian; Yang, Huifeng; Mei, Tao; Cao, Yi

doi:10.3892/etm.2022.11577

Cited by 16 publications

(12 citation statements)

References 101 publications

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“…37 Melanoma specimens resected from patients with refractory metastatic melanoma who were treated with nivolumab, a PD-1 inhibitor used for immunotherapy, exhibited high expression of interleukin 34 (IL-34). 38 Importantly, high expression of IL-34 was positively associated with an increased frequency of M2-polarized TAMs. 39 This finding suggests that M2-polarized TAMs may be related to resistance to PD-1 inhibitors in melanoma.…”

Section: Discussionmentioning

confidence: 95%

“…However, 25% of patients with melanoma who show an objective response to PD‐1 inhibitors develop resistance 37 . Melanoma specimens resected from patients with refractory metastatic melanoma who were treated with nivolumab, a PD‐1 inhibitor used for immunotherapy, exhibited high expression of interleukin 34 (IL‐34) 38 . Importantly, high expression of IL‐34 was positively associated with an increased frequency of M2‐polarized TAMs 39 .…”

Section: Discussionmentioning

confidence: 99%

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The clinicopathological impact of tumor‐associated macrophages in patients with cutaneous malignant melanoma

Asai,

Yanagawa,

Osakabe

et al. 2023

Journal of Surgical Oncology

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BackgroundTumor‐associated macrophages (TAMs) are an immune component of the cutaneous malignant melanoma (CMM) microenvironment and affect tumor growth. TAMs can polarize into different phenotypes, that is, proinflammatory M1 and anti‐inflammatory M2 macrophages. However, the role of the macrophage phenotype in CMM remains unclear.MethodsWe examined 88 patients with CMM. Tissue microarrays were constructed, and the density of M1 and M2 macrophages was analyzed by immunohistochemistry. Immune cells coexpressing CD68 and phosphorylated signal transducer and activator of transcription 1 (pSTAT1) were considered M1 macrophages, whereas those coexpressing CD68 and c‐macrophage activating factor (c‐Maf) were defined as M2 macrophages. These TAMs were counted, and the relationships between the density of M1 and M2 macrophages and clinicopathological factors including prognosis were investigated.ResultsThe CD68/c‐Maf score ranged from 0 to 34 (median: 5.5). The patients were divided based on the median score into the CD68/c‐Maf high (≥5.5) and low (<5.5) expression groups. Univariate and multivariate analyses revealed that CD68/c‐Maf expression was an independent predictive factor for progression‐free survival and an independent prognostic factor for overall survival. CD68/pSTAT1 expression was found in only two patients.ConclusionWe suggest that CD68/pSTAT1 coexpression is rarely observed in patients with CMM, and high CD68/c‐Maf expression is a predictor of worse prognosis in these patients.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

The clinicopathological impact of tumor‐associated macrophages in patients with cutaneous malignant melanoma

Asai,

Yanagawa,

Osakabe

et al. 2023

Journal of Surgical Oncology

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“…As innate immune cells, macrophages can kill tumor cells by phagocytosis, activation of T-cells, etc., leading to early elimination of tumor cells. However, numerous studies showed that macrophages play an important role in malignant diseases, being considered as pro-tumorigenic cells, by creating a microenvironment favorable to the multiplication and metastasis of tumor cells [ 45 , 46 , 47 ]. They interact with both tumor cells and stromal cells, secreting mediators (cytokines and chemokines) that favor angiogenesis, local invasion and blocking of the anti-tumor immune response [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of tumoral and peritumoral inflammatory reaction in cutaneous malignant melanomas

Fruntelată¹,

Bakri²,

Stoica³

et al. 2023

Rom J Morphol Embryol

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Skin cancer is one of the most common types of cancer, with an increasing worldwide incidence in recent decades. The main risk factor for increasing the skin cancer incidence is ultraviolet (UV) radiation. Of the two major forms of skin cancer (melanomas and non-melanotic cancers), the cutaneous melanoma (CM) is the most aggressive form, causing about 80% of the deaths resulted from this type of tumor. Malignant melanoma develops through malignant transformation of melanocytes in the skin because of prolonged exposure to solar or artificial UV. The malignant transformation of the melanocytes in the skin is accompanied by the presence of a local inflammatory reaction that, in the initial stages of carcinogenesis, would oppose to tumor development. Chronic exposure to UV or other etiopathogenic factors induces chronic inflammation, which, by producing inflammatory molecules (cytokines, chemokines, prostaglandins), constitutes a tumoral microenvironment that favors carcinogenesis, tumor invasion, metastasis, and the presence of neoplastic “mutant cells” that avoid the protective action of the immune system. Using immunohistochemistry techniques, we assessed the intra- and peritumoral inflammatory infiltrate cells in CM. The chronic inflammatory infiltrate presented more intense in the peritumoral stroma compared to the intratumoral one, heterogenous, more intensely composed of lymphocytes, plasma cells, macrophages, and mast cells (MCs), the most numerous cells in the inflammatory infiltrate being T-lymphocytes, plasma cells and macrophages; B-lymphocytes and MCs were in a small number, especially intratumorally. Inflammatory cells had a direct contact with tumor cells, blood vessels, connective matrix, suggesting that the inflammatory microenvironment plays an important role in carcinogenesis, tumor invasion, local angiogenesis, and tumor metastasis.

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“…In addition, M1 macrophages present antigens to T cells to enhance T-cell response. Thus, they are critical in defending against pathogens and tumor immunity [23,24]. M2 macrophages polarization occurs when exposed to the macrophage colony stimulating factor (MCSF), IL-10, tumor growth factor beta (TGF-β), and glucocorticoids.…”

Section: Roles Of Macrophages and Their Derived Exosomesmentioning

confidence: 99%

Recent advances in macrophage-derived exosomes as delivery vehicles

Wang¹,

Yang²,

Li³

et al. 2022

Nano TransMed

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Macrophages are important members of the innate immune system that can be reversibly polarized by different microenvironment signals. Exosomes secreted from cells are lipid bilayer membrane vesicles carrying versatile biomolecules, which displays unique properties and biological functions. Recent studies have shown that macrophage derived exosomes as an extracellular vehicle can deliver diverse cargoes including small molecules, nanoparticles, and biological macromolecules to recipient cells, and thus affect the progression of cancers and other diseases. Moreover, exosomes secreted by different phenotypes of macrophages provide different therapeutic options. Thus, in this review, we summarized recent progress in the macrophage derived exosomes as carriers for delivering different types of cargos. Then the engineering principles and their applications are elaborated. In the end, challenges and prospects of macrophage derived exosomes for drug delivery and disease treatment are also discussed.

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Macrophages in melanoma: A double‑edged sword and targeted therapy strategies (Review)

Cited by 16 publications

References 101 publications

The clinicopathological impact of tumor‐associated macrophages in patients with cutaneous malignant melanoma

The clinicopathological impact of tumor‐associated macrophages in patients with cutaneous malignant melanoma

Assessment of tumoral and peritumoral inflammatory reaction in cutaneous malignant melanomas

Recent advances in macrophage-derived exosomes as delivery vehicles

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