Development and Validation of a CD8+ T Cell Infiltration-Related Signature for Melanoma Patients

• Main Authors: Yuan Yuan, Zheng Zhu, Ying Lan, Saili Duan, Ziqing Zhu, Xi Zhang, Guoyin Li, Hui Qu, Yanhui Feng, Hui Cai, Zewen Song
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-05-01
• Series: Frontiers in Immunology
• Subjects: CD8+ T cells; melanoma; single cell RNA sequencing analysis; immunotherapy; immune response
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2021.659444/full

AimImmunotherapy shows efficacy in only a subset of melanoma patients. Here, we intended to construct a risk score model to predict melanoma patients’ sensitivity to immunotherapy.MethodsIntegration analyses were performed on melanoma patients from high-dimensional public datasets. The CD8+ T cell infiltration related genes (TIRGs) were selected via TIMER and CIBERSORT algorithm. LASSO Cox regression was performed to screen for the crucial TIRGs. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithm were used to evaluate the immune activity. The prognostic value of the risk score was determined by univariate and multivariate Cox regression analysis.Results184 candidate TIRGs were identified in melanoma patients. Based on the candidate TIRGs, melanoma patients were classified into three clusters which were characterized by different immune activity. Six signature genes were further screened out of 184 TIRGs and a representative risk score for patient survival was constructed based on these six signature genes. The risk score served as an indicator for the level of CD8+ T cell infiltration and acted as an independent prognostic factor for the survival of melanoma patients. By using the risk score, we achieved a good predicting result for the response of cancer patients to immunotherapy. Moreover, pan-cancer analysis revealed the risk score could be used in a wide range of non-hematologic tumors.ConclusionsOur results showed the potential of using signature gene-based risk score as an indicator to predict melanoma patients’ sensitivity to immunotherapy.