AUTHOR=Luo Wenjie , Wang Jin , Dai Xiaoyan , Zhang Hailiang , Qu Yuanyuan , Xiao Wenjun , Ye Dingwei , Zhu Yiping 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.754845

DOI=10.3389/fonc.2021.754845

ISSN=2234-943X

ABSTRACT=<sec><title>Objective</title><p>This study aimed to explore the role of <italic>ACSL4</italic> in CD8+ T cell tumor infiltration and outcomes of bladder cancer (BLCA) patients after immunotherapy.</p></sec><sec><title>Methods</title><p>The correlation between <italic>ACSL4</italic> expression and tumor infiltration of immune cells was analyzed using the Tumor Immune Estimation Resource database. The prognostic significance of <italic>ACSL4</italic> in BLCA was analyzed using Kaplan–Meier curves. Immunohistochemistry was used to detect CD8+ T cell infiltration in tumors with high and low <italic>ACSL4</italic> 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 <italic>ACSL4</italic> were explored using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathway analyses.</p></sec><sec><title>Results</title><p>The expression level of <italic>ACSL4</italic> was significantly correlated with the infiltration of CD8+ T cells in BLCA tumors (r = 0.192, P = 2.22e-04). Elevated <italic>ACSL4</italic> was associated with suppressed tumor progression and better outcomes for BLCA patients. The higher expression level of <italic>ACSL4</italic> predicted better immunotherapeutic responses and was associated with higher expression levels of core immune checkpoint genes, including <italic>CD274</italic>, <italic>CTLA4</italic>, <italic>PDCD1</italic>, and <italic>LAG3</italic>, compared with the low <italic>ACSL4</italic> expression group.</p></sec><sec><title>Conclusion</title><p>This study demonstrated for the first time that elevated <italic>ACSL4</italic> correlated significantly with CD8+ T cell infiltration and contributed to better immunotherapeutic responses in BLCA patients. Furthermore, <italic>ACSL4</italic> serves as a novel biomarker for predicting patient outcomes after immunotherapeutic treatments, which may improve the development of individualized immunotherapy for BLCA.</p></sec>