PD-L1 expression, immune cell correlates, and PD-1+ lymphocytes in sentinel lymph node positive melanoma patients: Implications for adjuvant PD-1 clinical trials.

e20011 Background: Patients with positive sentinel lymph node biopsies (SLNB) that undergo a completion lymphadenectomy have variable five-year survival rates ranging from 39-70%. PD-1 and PD-L1 inhibitors have significantly improved recurrence free (RFS) and overall survival (OS) in AJCC stage IIIC/IV metastatic melanoma patients. The aims of this study were to characterise subpopulations of lymphocytes that interact with metastatic melanoma cells in SLNB, to determine tumoral PD-L1 expression and to identify whether the PD-1/PD-L1 pathway contributes to immune escape in these patients to provide a rationale for the use of anti-PD-1 inhibitors in the adjuvant setting and aid in the selection of patients for this treatment modality. Methods: The metastatic melanoma containing SLNB’s from sixty treatment-naive patients were analysed for CD3, CD4, CD8, FOXP3, PD-1, and PD-L1 and correlated clinico-pathologic features and outcome. Results: Tumoral PD-L1 expression ( ≥ 1%-cutoff) was present in 43.3% (n = 26) cases. Cox proportional hazard analysis showed a positive correlation between intratumoral CD3+ lymphocytes and RFS/OS (cutoff > 39.5,HR = 0.36(0.17-0.76),p = 0.005;HR = 0.29(0.14-0.61),p = 0.0005,respectively), a positive correlation between intratumoral CD4+ lymphocytes and RFS/OS (cutoff > 24,HR = 0.34(0.15-0.77),p = 0.007;HR = 0.32(0.14-0.74),p = 0.005,respectively) and a positive correlation between intratumoral CD8+ lymphocytes and RFS/OS (cutoff > 29,HR = 0.42(0.21-0.85),p = 0.013;HR = 0.32(0.19-0.78),p = 0.006respectively) in our cohort of patients. There was a negative correlation between peritumoral PD-1+ lymphocytes and RFS/OS (cutoff > 1.5,HR = 2.67(1.17-6.13),p = 0.016;HR = 2.74(1.14-6.76),p = 0.019respectively). Conclusions: Expression of PD-L1 in metastatic melanoma-positive SLNB’s provides a rationale for trials of anti-PD-1 therapy in AJCC stage IIIA melanoma patients, particularly those with peritumoral PD-1+ lymphocytes. The expression of immune markers may also be useful to predict the outcome of patients following a positive SNLB.