Abstract 3119: A novel tissue resident memory T cell (TRM) signature predicts prognosis and tumor microenvironment of patients with melanoma

Abstract

Abstract Background: Melanoma is a prime example of how basic and translational research can improve cancer prognosis The tumor immune microenvironment (TIME) of melanoma is a dynamic, heterogeneous mixture of multiple immune cells and malignant and nonmalignant cells. Tissue resident memory T cells (TRM) may be prognostic for improved melanoma survival and proliferate during treatment with immune checkpoint inhibitors. The role of TRM in melanoma and rare melanoma subtypes is unknown. Method: Our goal was to examine the relationship between TRM abundance and melanoma prognosis. We generated TRM signatures using multiple independent single-cell RNA sequencing data from human melanoma cells to infer TRM abundance. Lastly, we built a LASSO Cox regression model that predicts patient survival. The TCGA dataset was used as a test group. Model accuracy was validated using Kaplan-Meier survival analysis, receiver operating characteristic curves, principal component analysis, and t-distributed stochastic neighbor embedding. Findings: We found a significantly longer overall survival in patients with high TRM infiltration. Furthermore, we found that TRM can interact with the tumor microenvironment and genomic features of melanoma, making TRM abundance positively correlate with the prognosis of melanoma patients. Melanoma abundance was also significantly associated with several common genomic aberrations, including the TP53 mutation. In addition, we developed a 20-gene risk score that significantly classifies patients into low- and high-risk categories. We found that in several independent datasets, patients with high risk scores had significantly worse overall survival than patients with low risk scores. Conclusions: Altogether, our findings suggest that TRM abundance may positively correlate with melanoma survival. We developed a high-precision LASSO Cox regression model based on the new TRM abundance characteristics. Our study shows that this model effectively predicts the prognosis of melanoma patients and may provide new therapeutic targets and measure the effectiveness of melanoma-directed therapies. Keywords: Tissue resident memory T cell, tumor immune microenvironment, melanoma, prognosis Citation Format: Chongming Jiang, Jianrong Li, Elena Helman, Xiling Shen, Chao Cheng. A novel tissue resident memory T cell (TRM) signature predicts prognosis and tumor microenvironment of patients with melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3119.