Table_2_ACSL4 Expression Is Associated With CD8+ T Cell Infiltration and Immune Response in Bladder Cancer.docx

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.

本项研究旨在探讨ACSL4在CD8+ T细胞肿瘤浸润及膀胱癌（BLCA）患者免疫治疗后预后中的作用。研究方法包括：利用肿瘤免疫估计资源数据库分析ACSL4表达与肿瘤浸润免疫细胞之间的相关性；采用Kaplan-Meier曲线分析ACSL4在BLCA中的预后意义；通过免疫组化技术检测来自复旦大学附属肿瘤医院患者肿瘤组织中高、低ACSL4表达肿瘤的CD8+ T细胞浸润情况；利用癌症基因组图谱和IMvigor 210队列分析免疫检查点基因与免疫反应之间的关系；通过京都基因与基因组百科全书（KEGG）和基因本体富集途径分析探讨ACSL4涉及到的分子功能、细胞组分和生物学过程。研究结果发现，ACSL4的表达水平与BLCA肿瘤中CD8+ T细胞的浸润程度显著相关（r = 0.192，P = 2.22e-04）。ACSL4的高表达与肿瘤进展的抑制及BLCA患者预后改善相关。ACSL4的高表达水平预示着更好的免疫治疗效果，并且与核心免疫检查点基因（如CD274、CTLA4、PDCD1和LAG3）的高表达相关，较之低ACSL4表达组。结论：本研究首次证实了ACSL4高表达与CD8+ T细胞浸润的显著相关性，并有助于BLCA患者免疫治疗效果的提升。此外，ACSL4作为一种新型生物标志物，有望预测免疫治疗后患者的预后，从而可能推动针对BLCA的个性化免疫治疗的发展。