BACKGROUND: As melanoma treatment options in the adjuvant setting continue to mature, major questions remain unanswered including which melanoma patients are likely to relapse and would therefore benefit from adjuvant treatments. In this study we aim to identify a signature of prognostic biomarkers including tumour infiltrating lymphocytes (TILs), the presence of tertiary lymphoid structures (TLS) and the circulating tumour–associated antigen (TAA) and cancer-testis antigen (CTA) antibodies to better predict relapse in stage III patients at diagnosis.
METHOD: We have utilised archival tumour and plasma samples from 128 stage III melanoma patients at their initial diagnosis who were enrolled in the Melanoma Research Victoria (MRV) project. We measured TAA and CTA antibodies using a novel protein microarray platform (CT100+ array) with patients’ plasma. We also performed Tyramide Signal Amplification (TSA)-Based multiplex immunohistochemistry (mIHC) with 6 markers on a single formalin-fixed paraffin-embedded tissue section to identify and quantify TILs and TLSs.
RESULTS: TAA and CTA antibody profiling of plasma samples revealed a signature of 6 prognostic tumour antigens of interest which can predict relapse with 74% sensitivity and 66% specificity (AUC=0.80). We have also developed a mIHC panel of immune markers consisting of CD3, CD19, Foxp3, CD68, CD45, and melanoma. Furthermore, we developed a panel with TLS associated markers including peripheral node addressin (PNAd), CD19, CD4, CD8, DC-LAMP and melanoma.
CONCLUSION: Combination of TAA and CTA antibody biomarkers along with a better understanding of the heterogeneous nature of TIL populations and the presence of TLSs in melanoma can inform patient prognosis.