Visualizing murine breast and melanoma tumor microenvironment using intravital multiphoton microscopy

PurposeTo identify CD8+ T cell-related factors and the co-expression network in melanoma and illustrate the interactions among CD8+ T cell-related genes in the melanoma tumor microenvironment.MethodWe obtained melanoma and paracancerous tissue mRNA matrices from TCGA-SKCM and GSE65904. The CIBERSORT algorithm was used to assess CD8+ T cell proportions, and the “estimate” package was used to assess melanoma tumor microenvironment purity. Weighted gene co-expression network analysis was used to identify the most related co-expression modules in TCGA-SKCM and GSE65904. Subsequently, a co-expression network was built based on the joint results in the two cohorts. Subsequently, we identified the core genes of the two most relevant modules of CD8+T lymphocytes according to the module correlation, and constructed the signature using ssGSEA. Later, we compared the signature with the existing classical pathways and gene sets, and confirmed the important prognostic significance of the signature in this paper.ResultsNine co-expressed genes were identified as CD8+ T cell-related genes enriched in the cellular response to interferon−gamma process and antigen processing and presentation of peptide antigen. In the low expression level group, inflammation and immune responses were weaker. Single-cell sequencing and immunohistochemistry indicated that these nine genes were highly expressed in CD8+ T cells group.ConclusionWe identified nine-gene signature, and the signature is considered as the biomarker for T lymphocyte response and clinical response to immune checkpoint inhibitors for melanoma

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p32 promotes melanoma progression and metastasis by targeting EMT markers, Akt/PKB pathway, and tumor microenvironment

Cell Death and Disease ◽

10.1038/s41419-021-04311-5 ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Sunita Sinha ◽

Satyendra Kumar Singh ◽

Nitish Jangde ◽

Rashmi Ray ◽

Vivek Rai

Keyword(s):

Tumor Microenvironment ◽

Human Melanoma ◽

Migration And Invasion ◽

Therapy Failure ◽

Melanoma Tumor ◽

Melanoma Progression ◽

Emt Markers

AbstractMelanoma originates from melanin-producing cells called melanocytes. Melanoma poses a great risk because of its rapid ability to spread and invade new organs. Cellular metastasis involves alteration in the gene expression profile and their transformation from epithelial to mesenchymal state. Despite of several advances, metastatic melanoma being a key cause of therapy failure and mortality remains poorly understood. p32 has been found to be involved in various physiological and pathophysiological conditions. However, the role of p32 in melanoma progression and metastasis remains underexplored. Here, we identify the role of p32 in the malignancy of both murine and human melanoma. p32 knockdown leads to reduced cell proliferation, migration, and invasion in murine and human melanoma cells. Furthermore, p32 promotes in vitro tumorigenesis, inducing oncogenes and EMT markers. Mechanistically, we show p32 regulates tumorigenic and metastatic properties through the Akt/PKB signaling pathway in both murine and human melanoma. Furthermore, p32 silencing attenuates melanoma tumor progression and lung metastasis in vivo, modulating the tumor microenvironment by inhibiting the angiogenesis, infiltration of macrophages, and leukocytes in mice. Taken together, our findings identify that p32 drives melanoma progression, metastasis, and regulates the tumor microenvironment. p32 can be a target of a novel therapeutic approach in the regulation of melanoma progression and metastasis.

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