Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/19207
Title: Altered Expression and Splicing of ESRP1 in Malignant Melanoma Correlates with Epithelial-Mesenchymal Status and Tumor-Associated Immune Cytolytic Activity.
Authors: Yao, Jun;Caballero, Otavia L;Huang, Ying;Lin, Calvin;Rimoldi, Donata;Behren, Andreas;Cebon, Jonathan S;Hung, Mien-Chie;Weinstein, John N;Strausberg, Robert L;Zhao, Qi
Affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Ludwig Collaborative Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland. Orygen Biotecnologia, SA., São Paulo, SP, Brazil
Regeneron Pharmaceuticals Inc., Tarrytown, New York
Clinical Tumor Biology and Immunotherapy Unit, Ludwig Center, University of Lausanne, Switzerland, Lausanne, Switzerland
Cancer Immunobiology Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Ludwig Cancer Research, New York, New York
Ludwig Collaborative Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland. Regeneron Pharmaceuticals Inc., Tarrytown, New York
Issue Date: Jun-2016
EDate: 2016-04-04
Citation: Cancer immunology research 2016; 4(6): 552-561
Abstract: Melanoma is one of the major cancer types for which new immune-based cancer treatments have achieved promising results. However, anti-PD-1 and anti-CTLA-4 therapies are effective only in some patients. Hence, predictive molecular markers for the development of clinical strategies targeting immune checkpoints are needed. Using The Cancer Genome Atlas (TCGA) RNAseq data, we found that expression of ESRP1, encoding a master splicing regulator in the epithelial-mesenchymal transition (EMT), was inversely correlated with tumor-associated immune cytolytic activity. That association holds up across multiple TCGA tumor types, suggesting a link between tumor EMT status and infiltrating lymphocyte activity. In melanoma, ESRP1 mainly exists in a melanocyte-specific truncated form transcribed from exon 13. This was validated by analyzing CCLE cell line data, public CAGE data, and RT-PCR in primary cultured melanoma cell lines. Based on ESRP1 expression, we divided TCGA melanoma cases into ESRP1-low, -truncated, and -full-length groups. ESRP1-truncated tumors comprise approximately two thirds of melanoma samples and reside in an apparent transitional state between epithelial and mesenchymal phenotypes. ESRP1 full-length tumors express epithelial markers and constitute about 5% of melanoma samples. In contrast, ESRP1-low tumors express mesenchymal markers and are high in immune cytolytic activity as well as PD-L2 and CTLA-4 expression. Those tumors are associated with better patient survival. Results from our study suggest a path toward the use of ESRP1 and other EMT markers as informative biomarkers for immunotherapy. Cancer Immunol Res; 4(6); 552-61. ©2016 AACR.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19207
DOI: 10.1158/2326-6066.CIR-15-0255
PubMed URL: 27045022
Type: Journal Article
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.