Exploring Tumor Immune Microenvironment and Its Associations With Molecular Characteristics in Melanoma

Abstract

BackgroundThe tumor microenvironment (TME), which involves infiltration of multiple immune cells into the tumor tissues, plays an essential role in clinical benefit to therapy. The chemokines and their receptors influence migration and functions of both tumor and immune cells. Also, molecular characteristics are associated with the efficacy of melanoma therapy. However, there lacked exploration of immune characteristics and the association with molecular characteristics.MethodsWe collected the currently available 569 melanoma samples that had both the genomic and transcriptional data from TCGA and SRA databases. We first identified TME subtypes based on the developed immune signatures, and then divided the samples into two immune cohorts based on the immune score. Next, we estimated the compositions of the immune cells of the two cohorts, and performed differential expression genes (DEGs) and functional enrichments. In addition, we investigated the interactions of chemokines and their receptors under immune cells. Finally, we explored the genomic characteristics under different immune subtypes.ResultsTME type D had a better prognosis among the four subtypes. The high-immunity cohort had significantly high 16 immune cells. The 63 upregulated and 384 downregulated genes in the high-immunity cohort were enriched in immune-related biological processes, and keratin, pigmentation and epithelial cells, respectively. The correlations of chemokines and their receptors with immune cell infiltration, such as CCR5-CCL4/CCL5 and CXCR3-CXCL9/CXCL10/CXCL11/CXCL13 axis, showed that the recruitments of 11 immune cells, such as CD4T cells and CD8T cells, were modulated by chemokines and their receptors. The proportions of the four TME subtypes in each molecular subtype were comparable. The two driver genes, CDKN2A and PRB2, had significantly different MAFs between the high-immunity and low-immunity.ConclusionWe dissected the characteristics of immune infiltration, the interactions of chemokines and their receptors under immune cells, and the correlation of molecular and immune characteristics. Our work will enable the reasonable selection of anti-melanoma treatments and accelerate the development of new therapeutic strategies for melanoma.

Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns

“…Different approaches to melanoma subtyping were already reported [41,42], although they were generally based on genomics or cancer cell histology. Wide exploratory studies addressing the immune aspects of melanoma TME were mostly solely computational [43][44][45], yet often meticulous and conclusive. The conventional and more supervised approaches, like ours, taking advantage of publicly available transcriptomic datasets also existed [46,47]; however, they usually carried different subtype annotations for what we believe could be recognized as immune desert, excluded, and inflamed tumors based on their biological information.…”

CT-based machine learning radiomics predicts CCR5 expression level and survival in ovarian cancer

“…Accurate prediction of prognosis is pivotal for the management of ovarian cancer. CCR5 as a chemokines' receptor, which may promote invasion and metastasis [6], has been actively investigated in various cancers [7][8][9][10][11][12][13]. Although limited in the field of ovarian cancer, several studies reported that CCR5 might be associated with prognosis [19,20].…”

“…The C-C motif chemokine receptor type 5 (CCR5) is one of the G protein-coupled receptors on leukocyte surfaces and is involved in the process of host immune response, which serves as our main defense against pathogens. Emerging evidence indicates CCR5 contributes largely to the tumor invasion and metastasis [6]. High expression of CCR5 causes tumor cell migration and vascular invasion, which can result in distant metastasis of several types of tumors such as breast cancers [7][8][9], hepatocellular carcinoma [10] and prostate cancers [11][12][13].…”

An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer

“…It encompasses the body's ability to recognize and mount a defense against cancer cells, as well as the strategies that tumors employ to evade immune surveillance. The tumor microenvironment (TME) is the area surrounding a tumor inside the body and comprising an extracellular matrix, blood vessels, fibroblasts, immune cells, inflammatory mediators, e.g., chemokines and cytokines, and others [59][60][61]. The dysregulated control of inflammation contributes to the initiation, promotion, and metastasis of cancer.…”