Comprehensive analysis of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2): A potential novel pan-cancer immune checkpoint

Kun-Hao Bai; Yi-Yang Zhang; Xue-Ping Li; Xiao-Peng Tian; Meng-Meng Pan; Da-Wei Wang; Yu-Jun Dai

doi:10.1016/j.csbj.2022.09.021

Comprehensive analysis of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2): A potential novel pan-cancer immune checkpoint

Comput Struct Biotechnol J. 2022 Sep 17:20:5226-5234. doi: 10.1016/j.csbj.2022.09.021. eCollection 2022.

Authors

Kun-Hao Bai^{1

2}, Yi-Yang Zhang^{1

2}, Xue-Ping Li^{1

3}, Xiao-Peng Tian⁴, Meng-Meng Pan⁵, Da-Wei Wang⁵, Yu-Jun Dai^{1

3}

Affiliations

¹ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 500020, Guangdong, China.
² Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, 500026, China.
³ Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou 500020, Guangdong, China.
⁴ Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
⁵ National Research Center for Translational Medicine, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 197, Ruijin Road II, Shanghai 200025, China.

Abstract

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.

Keywords: BLCA, Bladder Urothelial Carcinoma; BRCA, Breast invasive carcinoma; CESC, Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, Cholangiocarcinoma; COAD, Colon adenocarcinoma; ESCA, Esophageal carcinoma; GBM, Glioblastoma multiforme; HNSC, Head and Neck squamous cell carcinoma; Immune cell infiltration; KICH, Kidney Chromophobe; KIRC, Kidney renal clear cell carcinoma; KIRP, Kidney renal papillary cell carcinoma; LAML, Acute Myeloid Leukemia; LGG, Lower Grade Glioma; LIHC, Liver hepatocellular carcinoma; LUAD, Lung adenocarcinoma; LUSC, Lung squamous cell carcinoma; MESO, Mesothelioma; New immune checkpoint; OV, Ovarian serous cystadenocarcinoma; PAAD, Pancreatic adenocarcinoma; PCPG, Pheochromocytoma and Paraganglioma; PRAD, Prostate adenocarcinoma; Pan-cancer; READ, Rectum adenocarcinoma; SARC, Sarcoma; SKCM, Skin Cutaneous Melanoma; STAD, Stomach adenocarcinoma; Stemness feature; TGCT, Testicular Germ Cell Tumor; THCA, Thyroid carcinoma; THYM, Thymoma; TIPE2; UCEC, Uterine Corpus Endometrial Carcinoma; UCS, Uterine Carcinosarcoma; UVM, Uveal Melanoma.