Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, China.
Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Key Laboratory of Precision Diagnosis and Treatment of GastrointestinalTumors (China Medical University), Ministry of Education, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Shenyang, 110122, Liaoning Province, China.
BMC Cancer. 2023 Jun 9;23(1):528. doi: 10.1186/s12885-023-11015-w.
New immunotherapeutic strategies based on predictors are urgently needed. Toll-like receptor adaptor interacting with SLC15A4 on the lysosome (TASL) was recently confirmed to fulfill an important role in the innate immune response. However, whether TASL is involved in tumor development and immunotherapy response prediction has not been reported.
TCGA and GTEx were used to yield transcriptional, genetic, and epigenetic levels of TASL in 33 cancer types. CIBERSORT was used to explore the correlation between TASL expression and multiple immune-related signatures and tumor-infiltrating immune cell content in different cancer types. The ability of TASL to predict tumor immunotherapy response was analyzed in seven datasets. Finally, we tested TASL expression in human glioma cell lines and tissue samples and analyzed its correlation with clinicopathological parameters.
TASL is widely heterogeneous at the transcriptional, genetic, and epigenetic levels. High TASL expression is an independent poor prognostic factor for immune "cold" tumor Low-Grade Glioma (LGG) but an opposite factor for "hot" tumors Lung Adenocarcinoma (LUAD) and Skin Cutaneous Melanoma (SKCM). TASL may affect tumor immune infiltration by mediating tumor-infiltrating lymphocytes and tumor-associated macrophages. It may differentially affect the prognosis of the three cancers by regulating the immunosuppressive microenvironment in LGG and the immunostimulatory microenvironment in LUAD and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in cancers such as SKCM and was also experimentally confirmed to be positively associated with adverse clinicopathological features of gliomas.
TASL expression is an independent prognostic factor for LGG, LUAD, and SKCM. High TASL expression is a potential biomarker for the positive response to immunotherapy in certain cancer types such as SKCM. Further basic studies focusing on TASL expression and tumor immunotherapy are urgently needed.
迫切需要基于预测因子的新型免疫治疗策略。最近证实，溶酶体上 Toll 样受体衔接子相互作用蛋白 SLC15A4（TASL）在先天免疫反应中发挥重要作用。然而，TASL 是否参与肿瘤发生和免疫治疗反应预测尚未报道。
使用 TCGA 和 GTEx 数据库获得 33 种癌症类型的 TASL 转录本、遗传和表观遗传水平数据。CIBERSORT 用于探索不同癌症类型中 TASL 表达与多种免疫相关特征和肿瘤浸润免疫细胞含量的相关性。在七个数据集分析 TASL 预测肿瘤免疫治疗反应的能力。最后，我们检测了人胶质瘤细胞系和组织样本中的 TASL 表达，并分析其与临床病理参数的相关性。
TASL 在转录本、遗传和表观遗传水平上广泛存在异质性。高 TASL 表达是免疫“冷”肿瘤低级别胶质瘤（LGG）的独立不良预后因素，但对“热”肿瘤肺腺癌（LUAD）和皮肤黑色素瘤（SKCM）则相反。TASL 可能通过调节肿瘤浸润淋巴细胞和肿瘤相关巨噬细胞来影响肿瘤免疫浸润。它可能通过调节 LGG 中的免疫抑制微环境和 LUAD 和 SKCM 中的免疫刺激微环境，从而对三种癌症的预后产生不同的影响。高 TASL 表达是 SKCM 等癌症对免疫治疗阳性反应的潜在生物标志物，实验也证实其与胶质瘤的不良临床病理特征呈正相关。
TASL 表达是 LGG、LUAD 和 SKCM 的独立预后因素。高 TASL 表达是 SKCM 等某些癌症对免疫治疗阳性反应的潜在生物标志物。迫切需要进一步开展聚焦 TASL 表达与肿瘤免疫治疗的基础研究。
