Mapping the single-cell landscape of acral melanoma and analysis of the molecular regulatory network of the tumor microenvironments

He, Zan; Xin, Zijuan; Yang, Qiong; Wang, Chen; Li, Meng; Rao, Wei; Du, Zhimin; Bai, Jia; Guo, Zixuan; Ruan, Xiuhang; Zhang, Zhaojun; Fang, Xiangdong; Zhao, Hua

doi:10.7554/elife.78616

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…Meanwhile, the immunosuppressive interaction between MIF and CD74 also occurred in the G1 group between TAMs and all subcluster T cells and DCs, but not in the G2 group (Figure 5b,c), which reveals the important role of MIF‐CD74 in tumor immune of BrM. Similarly, MDK−SDC1 and MDK–NCL ligation occur between C4_SCGB2A2s to DC subclusters, C4_SCGB2A2s to C3_CCR5, C3_CCR5 to DC subclusters, and C3_CCR5 to T cell subclusters, which shows the effect may lead to T cell exhaustion in another scRNA‐seq analysis 32 . Furthermore, APP−CD74 interaction was also found in the suppression of TAMs on T cell subclusters and disappeared in the G2 group.…”

Section: Resultsmentioning

confidence: 86%

“…Similarly, MDK−SDC1 and MDK–NCL ligation occur between C4_SCGB2A2s to DC subclusters, C4_SCGB2A2s to C3_CCR5, C3_CCR5 to DC subclusters, and C3_CCR5 to T cell subclusters, which shows the effect may lead to T cell exhaustion in another scRNA‐seq analysis. 32 Furthermore, APP−CD74 interaction was also found in the suppression of TAMs on T cell subclusters and disappeared in the G2 group.…”

Section: Resultsmentioning

confidence: 98%

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Single‐cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis

Zhou,

He,

Huang

et al. 2024

Thoracic Cancer

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BackgroundBreast cancer has the highest incidence rate of cancer worldwide, and brain metastases (BrM) are among the most malignant cases. While some patients have benefited from immune checkpoint inhibitors (ICIs), the complex anatomical structure of the brain and the heterogeneity of metastatic tumors have made it difficult to characterize the tumor immune microenvironment (TME) of metastatic tumors.MethodsTo address this, we used single‐cell RNA sequencing (scRNA‐seq) to analyze immune cells in the cerebrospinal fluid (CSF) of BrM patients with breast cancer, thereby providing a comprehensive view of the immune microenvironment landscape of BrM.ResultsBased on canonical marker genes, we identified nine cell types, and further identified their subtypes through differential expression gene (DEG) analysis. We compared the changes in cells and functions in the immune microenvironment of patients with different prognoses. Our analysis revealed a series of genes that promote tumor immune function (CCR5, LYZ, IGKC, MS4A1, etc.) and inhibit tumor immune function (SCGB2A2, CD24, etc.).ConclusionsThe scRNA‐seq in CSF provides a noninvasive method to describe the TME of breast cancer patients and guide immunotherapy.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 98%

Single‐cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis

Zhou,

He,

Huang

et al. 2024

Thoracic Cancer

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“…After rigorous data quality control and preprocessing, 12517 cells meeting the inclusion criteria were selected for subsequent analyses. Based on the classical marker genes, [ 15 , 16 ] these cells were categorized into seven distinct cell types: melanoma cells (Slc45a2, Sox10, Tyr, Mlana, S100a1, Mitf, and S100b), macrophages (Cd68 and C1qa), T/NK cells (Cd3e, Cd3d, Ccl5, and Nkg7), fibroblasts (Lum and Pdgfra), monocytes (Cd14 and S100a9), endothelial cells (Pecam1), and other cells ( Figure 2 A,B ). The proportion of melanoma cells decreased, whereas the percentages of macrophages, T/NK cells, monocytes, and fibroblasts increased in the RT group (Figure 2C ).…”

Section: Resultsmentioning

confidence: 99%

Melanoma Derived Exosomes Amplify Radiotherapy Induced Abscopal Effect via IRF7/I‐IFN Axis in Macrophages

Wang,

Shen,

Gao

et al. 2024

Advanced Science

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Radiotherapy (RT) can induce tumor regression outside the irradiation field, known as the abscopal effect. However, the detailed underlying mechanisms remain largely unknown. A tumor‐bearing mouse model is successfully constructed by inducing both subcutaneous tumors and lung metastases. Single‐cell RNA sequencing, immunofluorescence, and flow cytometry are performed to explore the regulation of tumor microenvironment (TME) by RT. A series of in vitro assays, including luciferase reporter, RNA Pulldown, and fluorescent in situ hybridization (FISH) assays, are performed to evaluate the detailed mechanism of the abscopal effect. In addition, in vivo assays are performed to investigate combination therapy strategies for enhancing the abscopal effect. The results showed that RT significantly inhibited localized tumor and lung metastasis progression and improved the TME. Mechanistically, RT promoted the release of tumor‐derived exosomes carrying circPIK3R3, which is taken up by macrophages. circPIK3R3 promoted Type I interferon (I‐IFN) secretion and M1 polarization via the miR‐872‐3p/IRF7 axis. Secreted I‐IFN activated the JAK/STAT signaling pathway in CD8+ T cells, and promoted IFN‐γ and GZMB secretion. Together, the study shows that tumor‐derived exosomes promote I‐IFN secretion via the circPIK3R3/miR‐872‐3p/IRF7 axis in macrophages and enhance the anti‐tumor immune response of CD8+ T cells.

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“…Nevertheless, the common limitation of these studies at present is that most of the patients recruited were with cutaneous melanoma, with only 29 cases (8.63%) of the acral subtype in the CHECKMATE 238 trial [ 19 ]. Acral melanoma is the most common subtype in the Asian population including Chinese and Japanese [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Anti-PD-1 Immunotherapy versus Conventional Therapy for Stage III Melanoma: A Real-World Retrospective Cohort Study

Sun

et al. 2022

Pharmaceuticals

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The use of adjuvant therapy has provided survival benefits in patients with advanced melanoma. This study aimed to explore the recurrence and prognosis of the PD-1 inhibitor, conventional interferon (IFN), or observation (OBS) on resected stage III acral and cutaneous melanoma patients through a retrospective analysis. Patients with resected stage III melanoma at Fudan University Shanghai Cancer Center from 2017 to 2021 were enrolled with all of their clinicopathologic characteristics collected. They were divided into three groups: PD-1 inhibitor, IFN, and OBS. Survival analyses were performed to indicate the significance of different adjuvant therapies. A total of 199 patients were enrolled (PD-1 n = 126; IFN n = 31; and OBS n = 42), with their median follow-up times being 21 months, 24 months, and 49 months, respectively. The PD-1 inhibitor significantly improved relapse-free survival (p = 0.027) and overall survival (p = 0.033) compared with conventional treatment (IFN+OBS). The superiority of the PD-1 inhibitor was witnessed in stage IIIC/D (p = 0.000) acral (p = 0.05) melanoma patients with ulceration (p = 0.011) or lymph node macrometastasis (p = 0.010). The PD-1 inhibitor significantly reduced local recurrence and systemic metastasis compared with conventional therapy (p = 0.002). In conclusion, adjuvant anti-PD-1 immunotherapy can achieve better survival outcomes in acral and cutaneous melanoma patients compared with conventional treatment, without considering adverse events. More clinical benefits were seen in later-stage acral melanoma patients with ulceration or lymph node macrometastasis.

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Mapping the single-cell landscape of acral melanoma and analysis of the molecular regulatory network of the tumor microenvironments

Cited by 15 publications

References 56 publications

Single‐cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis

Single‐cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis

Melanoma Derived Exosomes Amplify Radiotherapy Induced Abscopal Effect via IRF7/I‐IFN Axis in Macrophages

Adjuvant Anti-PD-1 Immunotherapy versus Conventional Therapy for Stage III Melanoma: A Real-World Retrospective Cohort Study

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