Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma

Abstract

BackgroundCD8+ T cells work as a key effector of adaptive immunity and are closely associated with immune response for killing tumor cells. It is crucial to understand the role of tumor-infiltrating CD8+ T cells in uveal melanoma (UM) to predict the prognosis and response to immunotherapy.Materials and MethodsSingle-cell transcriptomes of UM with immune-related genes were combined to screen the CD8+ T-cell-associated immune-related genes (CDIRGs) for subsequent analysis. Next, a prognostic gene signature referred to tumor-infiltrating CD8+ T cells was constructed and validated in several UM bulk RNA sequencing datasets. The risk score of UM patients was calculated and classified into high- or low-risk subgroup. The prognostic value of risk score was estimated by using multivariate Cox analysis and Kaplan–Meier survival analysis. Moreover, the potential ability of gene signature for predicting immunotherapy response was further explored.ResultsIn total, 202 CDIRGs were screened out from the single-cell RNA sequencing of GSE139829. Next, a gene signature containing three CDIRGs (IFNGR1, ANXA6, and TANK) was identified, which was considered as an independent prognostic indicator to robustly predict overall survival (OS) and metastasis-free survival (MFS) of UM. In addition, the UM patients were classified into high- and low-risk subgroups with different clinical characteristics, distinct CD8+ T-cell immune infiltration, and immunotherapy response. Gene set enrichment analysis (GSEA) showed that immune pathways such as allograft rejection, inflammatory response, interferon alpha and gamma response, and antigen processing and presentation were all positively activated in low-risk phenotype.ConclusionOur work gives an inspiration to explain the limited response for the current immune checkpoint inhibitors to UM. Besides, we constructed a novel gene signature to predict prognosis and immunotherapy responses, which may be regarded as a promising therapeutic target.

PTPRO-related CD8+ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer

“…Given that TIME’s immune profile, including CD8 + T-cell-related genes, has been shown to correlate with prognosis ( 36 , 37 ), and based on PTPRO’s regulatory role in promoting CD8 + T-cell infiltration, we further investigated the association between CD8 + T-cell-related genes and PTPRO. By analyzing the scRNA-seq data from the GSE110686 cohort, 127 CD8 + T-cell marker genes were confirmed ( Figure 3A , Supplementary Figure S2A ).…”

Digital Quantification of Intratumoral CD8+ T-Cells Predicts Relapse and Unfavorable Outcome in Uveal Melanoma

“…Other evidence reinforced the relationship between immune cell infiltration and prognosis, with the exception of some genetically distinct subgroups [ 28 ]. Recently, a bioinformatic analysis and CD8+ gene signature confirmed the prognostic role of CD8 in UM [ 17 , 18 ]. In addition, a recent study performing single cell analyses of the tumor and the microenvironment in primary and metastatic UMs outlined genomic complexity, as well as revealing a different subset of CD8+ T cells expressing checkpoint marker LAG3 but not PD1 or CTLA4 [ 29 ].…”

“…In the context of UM, inflammatory cell infiltration has been described within and at the periphery of the tumor, especially when epithelioid cells are predominant [ 7 ]. High densities of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) in primary UM have been correlated with a higher metastasis risk and worse prognosis [ 16 , 17 , 18 ]. Previous studies have shown that most TAMs in UMs are M2-type cells expressing CD68+ and CD163+, and survival was significantly reduced among patients with a high M2 macrophage and T cell density [ 19 , 20 , 21 , 22 ].…”

The Immunological Contribution of a Novel Metabolism-Related Signature to the Prognosis and Anti-Tumor Immunity in Cervical Cancer

“…Biomarker-based patient stratification has gained much attention, which calls for more accurate evaluation of these molecular properties. Especially for those patients who receive immunotherapy, the comprehensive analysis of the risk score, as well as immune checkpoint expression, could hopefully foretell the reactivity of these patients and therefore screen out the appropriate patients for immunotherapy [32][33][34]. Immune checkpoints expressed on cancer cells or cancer-associated immune cells have drawn substantial attention as promising treatment targets nowadays [35].…”