M2 - An Immune Tolerant Sentinel Node Microenvironment Predicts Recurrence in Melanoma
Monday, February 17, 2020
7:30 AM – 7:45 AM
Location: Sebastian I 1/2
Background: While sentinel lymph node (SLN) biopsy is standardly used to identify patients at risk for melanoma recurrence, it fails to accurately risk stratify certain patients. Since processes in SLNs regulate anti-tumor immune responses, we hypothesize that SLN immune gene expression may distinguish patients at high risk.
Methods: NanoString nCounter® is an RNA-based technology that allows for quantification of multiplexed target molecules. The nCounter PanCancer Immune Profiling Panel was used to analyze expression of 730 genes in sixty SLN specimens (30 positive [pSLN], 30 negative [nSLN]) from a retrospective melanoma cohort. Stepwise variable selection for Cox regression models was used with alpha levels of 0.05 for insertion and 0.1 for deletion to identify genes differentially expressed in SLNs of patients with recurrence and develop a risk stratification model.
Results: At a median follow up of 6.3 years, 14 pSLN (46.7%) and 6 nSLN (20.0%) patients recurred. A model incorporating ten genes accurately predicted risk of recurrence (C-index 0.9919). Included in the model was increased expression of TIGIT, an immune checkpoint, and decreased expression of CXCL16, a cytokine important in promoting dendritic and T cell interactions. Independent of SLN status, a risk score calculated using these 10 genes successfully stratified patients into cohorts at high and low risk for recurrence with high concordance (log-rank p<0.001).
Conclusions: Sentinel node immune gene expression is associated with melanoma recurrence, which may be used to identify patients at high or low risk for recurrence regardless of SLN status, potentially enhancing patient selection for adjuvant therapy.