Oral Presentation 2015 Annual Meeting of the Australasian Society for Dermatology Research

Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases: implications for adjuvant checkpoint inhibitors (#31)

Hojabr Kakavand 1 2 , Ricardo Vilain 2 , James S Wilmott 1 2 , Jennifer H Yearley 3 , John F Thompson 1 2 , Peter Hersey 2 , Georgina V Long 1 2 , Richard A Scolyer 1 2
  1. University of Sydney, Camperdown, NSW, Australia
  2. Melanoma Institute Australia, North Sydney, NSW, Australia
  3. Merck Researc Laboratories, Palo Alto, California, USA

Purpose: Melanoma patients with sentinel lymph node (SLN) metastases have variable five-year survival rates (39-70%). Anti-PD-1/PD-L1 inhibitors have significantly improved clinical outcome in unresectable AJCC stage IIIC/IV metastatic melanoma patients, and are being trialed in the adjuvant setting in advanced stage disease. The aims of this study were, in SLNs, to characterize subpopulations of lymphocytes that interact with metastatic melanoma cells and analyze their associations with outcome, and to determine tumour PD-L1 expression to provide a rational scientific basis for the administration of adjuvant anti-PD-1/PD-L1 inhibitors in early stage metastatic melanoma.

Experimental Design: SLNs containing metastatic melanoma from sixty treatment-naive patients were analyzed for CD3, CD4, CD8, FOXP3, PD-1, and PD-L1. The results were correlated with clinico-pathologic features and outcome.

Results: Tumoural PD-L1 expression was present in 26 cases (43.3%) but did not correlate with outcome. However, positive correlations between the number of CD3+ tumor-infiltrating lymphocytes (TILs) and recurrence-free (RFS)/overall survival (OS) (HR=0.36 (0.17-0.76), p=0.005; HR=0.29 (0.14-0.61), p=0.0005, respectively), the number of CD4+ TILs and RFS/OS (HR=0.34 (0.15-0.77), p=0.007; HR=0.32 (0.14-0.74), p=0.005, respectively), and the number of CD8+ TILs and RFS/OS (HR=0.42 (0.21-0.85), p=0.013; HR=0.32 (0.19-0.78), p=0.006, respectively) were observed. There was a negative correlation between the number of peritumoral PD-1+ lymphocytes and RFS/OS (HR=2.67 (1.17-6.13), p=0.016; HR=2.74 (1.14-6.76), p=0.019, respectively).

Conclusions: Expression of PD-L1 in SLN melanoma metastases provides a rationale for anti-PD-1/PD-L1 therapy trials in AJCC stage IIIA melanoma patients, particularly those with peritumoral PD-1+ lymphocytes. The expression of immune markers and T-cell subsets predicts outcome of SLN-positive patients.