ACSL4 Expression Is Associated With CD8+ T Cell Infiltration and Immune Response in Bladder Cancer

Abstract

ObjectiveThis study aimed to explore the role of ACSL4 in CD8+ T cell tumor infiltration and outcomes of bladder cancer (BLCA) patients after immunotherapy.MethodsThe correlation between ACSL4 expression and tumor infiltration of immune cells was analyzed using the Tumor Immune Estimation Resource database. The prognostic significance of ACSL4 in BLCA was analyzed using Kaplan–Meier curves. Immunohistochemistry was used to detect CD8+ T cell infiltration in tumors with high and low ACSL4 expression obtained from patients at the Fudan University Shanghai Cancer Center. The relationships between immune checkpoint genes and immune response were analyzed using The Cancer Genome Atlas and IMvigor 210 cohorts. The molecular functions, cellular components, and biological processes involving ACSL4 were explored using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathway analyses.ResultsThe expression level of ACSL4 was significantly correlated with the infiltration of CD8+ T cells in BLCA tumors (r = 0.192, P = 2.22e-04). Elevated ACSL4 was associated with suppressed tumor progression and better outcomes for BLCA patients. The higher expression level of ACSL4 predicted better immunotherapeutic responses and was associated with higher expression levels of core immune checkpoint genes, including CD274, CTLA4, PDCD1, and LAG3, compared with the low ACSL4 expression group.ConclusionThis study demonstrated for the first time that elevated ACSL4 correlated significantly with CD8+ T cell infiltration and contributed to better immunotherapeutic responses in BLCA patients. Furthermore, ACSL4 serves as a novel biomarker for predicting patient outcomes after immunotherapeutic treatments, which may improve the development of individualized immunotherapy for BLCA.

Impact of ACSL4 on the prognosis of hepatocellular carcinoma: Association with cancer‐associated fibroblasts and the tumour immune microenvironment

“…31,32 In a previous report related to tumour immunity, ACSL4 was reported to be associated with CD8 + T cell infiltration in bladder cancer and ACSL4 correlated with T cell signatures and improved survival in immune check inhibitor-treated cancer patients. 33,34 Contrary to these reports, our results using a public database and our cohorts showed that ACSL4 expression correlated with Foxp3 + TILs. We speculate that SREBP1 activation by ACSL4 may promote Treg expression.…”

A Novel Predictive Model for Adrenocortical Carcinoma Based on Hypoxia- and Ferroptosis-Related Gene Expression

“…Cheng et al found that ACSL4 suppresses glioma cell proliferation by activating ferroptosis ( 43 ). Luo et al found that higher ACSL4 expression was associated with CD8+ T cell infiltration and immune response in bladder cancer ( 44 ). FANCD2 is a nuclear protein involved in DNA damage repair and has been found to protect against ferroptosis ( 45 ).…”

ACSL3 and ACSL4, Distinct Roles in Ferroptosis and Cancers

“…This study further found that higher ferroptosis levels in CD8 + T cells enhanced their antitumor function and CD36 − CD8 + T cells combined with PD-1 antibodies showed better antitumor effect and survival time, suggesting that targeting ferroptosis is a promising therapy for improving immune checkpoint blockade (ICB)-based tumor immunotherapy. It has been shown that ACSL4 expression is significantly correlated with the amount of CD8 + T cells present in bladder cancer (BLCA) [ 80 ]. Patients with BLCA and elevated ACSL4 levels had better prognoses and suppressed tumor progression.…”