Moucheng Zhang,1–3 Zhilong Yan,2 Junjiang Wang,1,3 Xueqing Yao1,3 1Second Clinical Medical College of Southern Medical University, Guangzhou, 2Department of Gastrointestinal Surgery, First Hospital of Ningbo, Ningbo, Zhejiang, 3Department of General Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China Background: Toll-like receptors (TLRs) play a critical role in cancer, yet the clinical relevance of TLR7/8 expression in melanoma remains unclear. This study aimed to evaluate the prognostic value of TLR7/8 mRNA levels in melanoma and their correlation with immune biomarkers relevant to disease progression.Methods: Normalized gene expression and corresponding clinical data of patients with skin cutaneous melanoma were obtained from two public databases: the Cancer Genome Atlas and GSE19234. Log rank (Mantel–Cox) tests were used to perform survival analysis. Multivariate survival analysis was performed on a Cox-regression hazard model. Spearman correlation analyses were used to address the relationship between the expressions of TLR7/8 levels and immune biomarkers in melanoma tumors.Results: Survival analysis suggested that high levels of TLR7 or TLR8 expression predicted better clinical outcome for melanoma patients (TLR7: HR =1.734, P<0.0001; TLR8: HR =2.072, P<0.0001). Moreover, multivariate survival analysis implicated TLR7 as a prognostic factor independent of age, gender, or pathological stage. Further analysis demonstrated that expression levels of TLR7/8 strongly correlated with that of dendritic cell markers and chemokines/chemokine receptors, including CCR2, CCR5, CCL3, and CCL5. Importantly, expression levels of both TLR7 and TLR8 were also highly correlated with the expressions of CD8 and other functional markers of CD8+ T cells.Conclusion: High gene expression of TLR7 and TLR8 in melanoma tumors is associated with high expression levels of functional markers of immune cells, which predicts longer overall survival of patients with melanoma. Our results not only provide an important reference for the clinical prognosis of melanoma but also present new implications for the design of melanoma immunotherapy. Keywords: TLR7, TLR8, melanoma, prognosis, survival, immune marker, immunotherapy