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 expression of ESRP1, encoding a master splicing regulator in the epithelial-to-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 five percent 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.
Copyright ©2016, American Association for Cancer Research (AACR) (Free AACR Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!