Correlation of tumor-infiltrating immune cells of melanoma with overall survival by immunogenomic analysis

Cancer Med. 2020 Nov;9(22):8444-8456. doi: 10.1002/cam4.3466. Epub 2020 Sep 15.

Abstract

Aims: Different types of tumor-infiltrating immune cells not only augment but also dampen antitumor immunity in the microenvironment of melanoma. Therefore, it is critical to provide an overview of tumor-infiltrating immune cells in melanoma and explore a novel strategy for immunotherapies.

Methods: We analyzed the immune states of different stages in melanoma patients by the immune, stromal, and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) scores. Immune cell types were identified by the estimating relative subsets of RNA transcripts (CIBERSORTx) algorithm in 471 melanoma and 324 healthy tissues. Moreover, we performed a gene set variation analysis (GSVA) to determine the differentially regulated pathways in the tumor microenvironment.

Results: In melanoma cohorts, we found that ESTIMATE and immune scores were involved in survival or tumor clinical stage. Among the 22 immune cells, CD8+ T cells, M2 macrophages, and regulatory T cells (Tregs) showed significant differences using the CIBERSORTx algorithm. Furthermore, GSVA identified the immune cell-related pathways; the primary immunodeficiency pathway, intestinal immune network for IgA, and TGF-β pathways were identified as participants of the crosstalk in CD8+ T cells, Tregs, and M2 macrophages in the melanoma microenvironment.

Conclusion: These results reveal the cellular and molecular characteristics of immune cells in melanoma, providing a method for selecting targets of immunotherapies and promoting the efficacy of therapies for the treatment of melanoma.

Keywords: CD8+ T cells; M2 macrophage; melanoma; tumor-infiltrating immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Immunogenetic Phenomena*
  • Immunogenetics*
  • Immunophenotyping
  • Immunotherapy
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Melanoma / genetics
  • Melanoma / immunology*
  • Melanoma / mortality
  • Melanoma / therapy
  • Neoplasm Staging
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Signal Transduction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / therapy
  • Time Factors
  • Transcriptome*
  • Tumor Microenvironment*
  • Tumor-Associated Macrophages / immunology*