Abstract
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.
Highlights
Melanoma, one of the most aggressive cancers, causes approximately 61,000 deaths worldwide annually, accounting for more than 80% of skin cancer-related deaths [1]
Based on the candidate T cell infiltration related genes (TIRGs), melanoma patients were classified into three clusters which were characterized by different immune activity
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
Summary
One of the most aggressive cancers, causes approximately 61,000 deaths worldwide annually, accounting for more than 80% of skin cancer-related deaths [1]. A positive correlation between CD8+ T cell infiltration and improved prognosis is observed in many other types of cancer [9,10,11], further highlighting a pivotal role of CD8+ T cells in tumor suppression. Immunotherapy with several checkpoint blockers targeting programmed cell death protein 1 (PD-1), PD-1 ligand (PDL1), or cytotoxic T lymphocyte antigen-4 (CTLA-4) has resulted in significant improvement in clinical outcomes of melanoma patients [14]. Another strategy of immunotherapy called CAR-T cell therapy shows promising effects in melanoma patients [15]. Generally containing tumor-specific antigens (TSA) or tumor associated antigens (TAA), serves as another approach to generate or amplify antitumor immunity [16, 17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
