February 24, 2022

Melanoma treatment response

Targeting the interaction between melanoma and immune cells could improve responses to targeted cancer therapies, Vanderbilt researchers found.

by Sarah E. Glass

Although targeted therapies have been developed for melanoma patients, tumor progression eventually results. Understanding characteristics of melanoma associated with treatment resistance is important for prolonging therapy effectiveness. 

In a retrospective study of patients treated with BRAF and/or MEK inhibitors, Chi Yan, PhD, Ann Richmond, PhD, and colleagues discovered an association between tumor progression and an increase in melanoma cells bearing SOX10, a protein required for melanoma tumor growth. 

Reporting in the journal npj Precision Oncology, the researchers found a close physical association of SOX10+ melanoma cells with CD8+ T cells correlated with shorter progression-free survival of patients treated with BRAF/MEK inhibitors.  

SOX10 had independent and added prognostic value for late- and early-stage melanoma, respectively: patients with high SOX10/low CD8 tumors had a worse overall survival than those with low SOX10/high CD8 tumors. 

While further research is needed, targeting the melanoma – T-cell interaction, particularly through exclusion of SOX10+ melanoma cells or reversion of T-cell suppression, potentially could prevent acquired resistance to BRAF/MEK-targeted therapy.

The research was supported in part by a Merit Award and Senior Research Career Scientist Award from the U.S. Department of Veterans Affairs, and National Institutes of Health grant CA116021.