Protective effect of a brisk tumor infiltrating lymphocyte infiltrate in melanoma: An EORTC melanoma group study

Abstract

8519 Background: Tumor-infiltrating lymphocytes (TILs) in melanoma are responsible for tumor killing and may induce spontaneous regression. Brisk TILs in the melanoma vertical growth phase (VGP) is a strong, albeit not independent, prognostic factor associated with superior survival. This study investigated whether more detailed classes of TIL patterns, based on topography and intensity, are independent prognostic factors and identify patients with good prognosis. Methods: The study included 1,171 patients with cutaneous VGP melanoma with at least 3 years of follow up for whom slides were available for review. TIL infiltrate was assessed for pattern (absent, non brisk, brisk), intensity (scanty, moderate, dense), and topography (peripheral, central, both). Pattern was assessed qualitatively: brisk TIL infiltrate was defined as a continuous band of lymphocytes at the base of the melanoma, or throughout the tumor. Other studied variables were: thickness, mitotic count (MC), ulceration, gender, age, anatomic site, melanoma-related death (MRD). Subsequently, Chi-square tests, Kaplan-Meier curves (KM), logrank tests, and Cox models were applied to examine the relation between MRD, TIL categories and interaction with other variables. Results: A brisk infiltrate was observed in 21.2% of the cases. Adjusted hazard ratio for MRD as compared to the absent category was 0.82 (95% CI=0.64–1.06) in the non-brisk category, and 0.43 (95% CI=0.28–0.68) in the brisk category. Based on the Cox model, brisk TIL was an independent prognostic factor for MRD (p<0.001) controlling for thickness, MC, ulceration, gender, age and site. Intensity was significantly associated with MRD for melanomas with peripheral and central brisk TILs (p=0.027) but not for other melanomas. Remarkably, no death was observed in the 5.5% of melanomas with dense, brisk TIL infiltrate at ten years. Conclusions: A brisk TIL pattern was shown to have prognostic value for MRD underscoring the importance of TILs in the outcome of VGP melanoma patients. Furthermore, we identified a small population of “super-responder” patients whose tumor was characterised by a continuous and dense TIL infiltrate and who did not display signs of tumor progression. No significant financial relationships to disclose.