Bai Kun-Hao, Zhang Yi-Yang, Li Xue-Ping, Tian Xiao-Peng, Pan Meng-Meng, Wang Da-Wei, Dai Yu-Jun
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 500020, Guangdong, China.
Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, 500026, China.
Comput Struct Biotechnol J. 2022 Sep 17;20:5226-5234. doi: 10.1016/j.csbj.2022.09.021. eCollection 2022.
Tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2) is encoded by TNFAIP8L2 and is a newly identified negative regulator of natural and acquired immunity that plays a critical function in maintaining immune homeostasis. Recently, CAR-NK immune cell therapy has been a focus of major research efforts as a novel cancer therapeutic strategy. TIPE2 is a potential checkpoint molecule for immune cell maturation and antitumor immunity that could be used as a novel NK cell-based immunotherapeutic approach. In this study, we explored the expression of TNFAIP8L2 across various tumor types and found that TNFAIP8L2 was highly expressed in most tumor types and correlated with prognosis. Survival analysis showed that TNFAIP8L2 expression was predictive of improved survival in cervical-squamous-cell-carcinoma (CESC), sarcoma (SARC) and skin-cutaneous-melanoma (SKCM). Conversely, TNFAIP8L2 expression predicted poorer survival in acute myeloid leukemia (LAML), lower-grade-glioma (LGG), kidney-renal-clear-cell-carcinoma (KIRC) and uveal-melanoma (UVM). Analysis of stemness features and immune cell infiltration indicated that TNFAIP8L2 was significantly associated with cancer stem cell index and increased macrophage and dendritic cell infiltration. Our data suggest that TNFAIP8L2 may be a novel immune checkpoint biomarker across different tumor types, particularly in LAML, LGG, KIRC and UVM, and may have further utility as a potential target for immunotherapy.
肿瘤坏死因子-α诱导蛋白8样2（TIPE2）由TNFAIP8L2编码，是一种新发现的天然免疫和获得性免疫的负调节因子，在维持免疫稳态中发挥关键作用。近年来，嵌合抗原受体自然杀伤细胞（CAR-NK）免疫细胞疗法作为一种新型癌症治疗策略一直是主要研究热点。TIPE2是免疫细胞成熟和抗肿瘤免疫的潜在检查点分子，可作为一种新型的基于自然杀伤细胞的免疫治疗方法。在本研究中，我们探究了TNFAIP8L2在各种肿瘤类型中的表达情况，发现TNFAIP8L2在大多数肿瘤类型中高表达且与预后相关。生存分析表明，TNFAIP8L2表达可预测宫颈鳞状细胞癌（CESC）、肉瘤（SARC）和皮肤黑色素瘤（SKCM）患者生存率提高。相反，TNFAIP8L2表达预示急性髓系白血病（LAML）、低级别胶质瘤（LGG）、肾透明细胞癌（KIRC）和葡萄膜黑色素瘤（UVM）患者生存率较差。干性特征和免疫细胞浸润分析表明，TNFAIP8L2与癌症干细胞指数以及巨噬细胞和树突状细胞浸润增加显著相关。我们的数据表明，TNFAIP8L2可能是不同肿瘤类型，尤其是LAML、LGG、KIRC和UVM中的一种新型免疫检查点生物标志物，并且可能作为免疫治疗的潜在靶点具有进一步的应用价值。
