Broad and Conserved Immune Regulation by Genetically Heterogeneous Melanoma Cells.

Details

Serval ID
serval:BIB_4F63C0C97A59
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Broad and Conserved Immune Regulation by Genetically Heterogeneous Melanoma Cells.
Journal
Cancer research
Author(s)
Neubert N.J., Tillé L., Barras D., Soneson C., Baumgaertner P., Rimoldi D., Gfeller D., Delorenzi M., Fuertes Marraco S.A., Speiser D.E.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Publication state
Published
Issued date
01/04/2017
Peer-reviewed
Oui
Volume
77
Number
7
Pages
1623-1636
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Although mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to T-cell-based immunotherapy. Here, we studied the reactions of malignant and benign melanocyte lines to cytotoxic CD8(+) T cells (CTL) using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune-regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα. These reactions were predominantly homogenous, independent of oncogenic driver mutations, and similar in benign and malignant cells. The reactions exhibited both pro- and antitumorigenic potential and primarily corresponded to mechanisms that were conserved, rather than acquired, by mutations. Similar results were obtained from direct ex vivo analysis of the tumor microenvironment. Thus, immune regulation in the tumor landscape may often be driven by conserved mechanisms, which may explain why T-cell-based immunotherapy can provide durable benefits with relatively infrequent escape. Cancer Res; 77(7); 1623-36. ©2017 AACR.

Keywords
Cell Line, Tumor, GTP Phosphohydrolases/genetics, Genetic Heterogeneity, Humans, Immunotherapy, Interferon-gamma/pharmacology, Lymphocyte Activation, Melanoma/immunology, Melanoma/therapy, Membrane Proteins/genetics, Mutation, Proto-Oncogene Proteins B-raf/genetics, T-Lymphocytes, Cytotoxic/immunology, Tumor Escape, Tumor Microenvironment, Tumor Necrosis Factor-alpha/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
30/01/2017 19:20
Last modification date
20/08/2019 14:05
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