Supplementary Material for: Prognostic Significance of Tumor-Infiltrating Lymphocyte Grade in Melanoma: A Meta-Analysis

Purpose: Tumor-infiltrating lymphocytes (TILs) in primary melanoma are considered to represent the host’s antitumor immune response; however, whether TILs can independently predict survival remains controversial. This meta-analysis evaluated the prognostic value of TIL grade for survival in patients with melanoma. Methods: We identified studies from the PubMed, Web of Science, and China National Knowledge Infrastructure databases to assess the prognostic impact of TIL grade in patients with melanoma. We estimated the combined hazard ratios (HRs) for overall survival (OS), disease-free survival, and disease-specific survival (DSS) at 5 years and end point using either fixed-effect or random-effect models depending on heterogeneity. Results: A total of 13 observational studies including 7,633 patients were enrolled. In the univariate analysis, brisk TIL grade was significantly more strongly correlated with better 5-year OS, 5-year DSS, and end point DSS compared with those of nonbrisk or absent TILs (HR 0.62, 95% CI 0.44–0.88, I² = 0; HR 0.53, 95% CI 0.30–0.96, I² = 11%; and HR 0.51, 95% CI 0.30–0.87, I² = 0, respectively). Compared with absent TIL grade, brisk TIL grade was associated with better 5-year OS and end point OS (HR 0.68, 95% CI 0.50–0.93, I² = 40% and HR 0.65, 95% CI 0.52–0.83, I² = 0, respectively). Nonbrisk TIL grade was associated with better end point DSS (HR 0.60, 95% CI 0.44–0.83, I² = 7%). The multifactor analysis showed that brisk TIL grade was related to better DSS (HR 0.50, 95% CI 0.30–0.90), and nonbrisk or absent TIL grade was correlated with poor DSS (HR 8.7, 95% CI 2.7–40.3). Conclusion: Patients with brisk TIL grade had a better prognosis. TIL level deserves further investigation to support the conclusion that it should be routinely included in the pathological report of primary melanoma and in future American Joint Committee on Cancer staging revisions.