074 Predicting recurrence in primary melanomas by T cell receptor immunosequencing

Intermediate risk primary melanomas (1-4mm) are potentially curable by resection but pose a risk of recurrence locally or metastatically. Factors used to try to predict recurrence include sentinel lymph node status, ulceration, rate of mitosis, and tumor infiltrating lymphocyte status measured histopathologically. High throughput sequencing (HTS) of the TCRB has been applied in metastatic melanoma and the characteristics of infiltrating T cell repertoire could be used as a predictive marker for response to immunotherapy. In this study we measured the T cell content of primary melanomas by HTS of the TCRB. T cell fraction (% of nucleated cells that are T cells) and T cell clonality were determined in 170 archival FFPE melanoma samples from patients followed for at least 5 years. T cell fraction was a robust independent variable to predict progression free (PFS) and overall survival, and was second only to Breslow thickness in its predictive value. In contrast, T cell clonality did not predict survival. By gradient boost modelling, Breslow thickness combined with T cell fraction yields a highly predictive tool for PFS. Interestingly, T cell infiltrate measured by TCR HTS did not correlate with TIL briskness described by histopathology. The PFS segregation by high vs low T cell infiltrate is also observable as a trend for clinically relevant subgroups of 1-2mm, 2-4mm and >4mm; this is currently being validated using additional samples. In addition to prognosis, it may be that intermediate thickness melanomas with high T cell infiltrate are ideal candidates for adjuvant immunotherapy to prolong their PFS.