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

Tumor necrosis factor -a-inducible protein 8-like 2 (TIPE2) is encoded by TNFAIP8L2 and is a newly iden-tified 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 matura-tion 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.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Automated summary

In this study, the expression of TNFAIP8L2 was explored across various tumor types and found to be highly expressed in most tumor types and correlated with prognosis. TNFAIP8L2 expression predicted improved survival in certain tumors, while poorer survival in others. Furthermore, TNFAIP8L2 was significantly associated with cancer stem cell index and increased immune cell infiltration. Therefore, TNFAIP8L2 may serve as a novel immune checkpoint biomarker across different tumor types and could be a potential target for immunotherapy.