Targeting TNFAIP2 induces immunogenic cell death and sensitizes glioblastoma multiforme to anti-PD-1 therapy.

Autor: Hou, Chongxian, Shi, Shenbao, Gao, Mengjiao, Ji, Jingsen, Ma, Chengcheng, Wang, Tianwei, Chen, Taoliang, Liu, Yang, Zhong, Jiasheng, Zheng, Yaofeng, Ye, Jing'an, Ke, Yiquan
Zdroj: Journal of Neuro-Oncology; Oct2023, Vol. 165 Issue 1, p79-90, 12p
Abstrakt: Background: The efficacy of current immunotherapeutic strategies for patients with glioblastoma multiforme (GBM) remains unsatisfactory. The purpose of this study was to investigate the correlation between tumor necrosis factor alpha-induced protein 2 (TNFAIP2) and immunogenic cell death (ICD) in GBM, and to examine the effect of TNFAIP2 knockdown and anti-PD-1 combination treatment in a mouse glioma model. Methods: The CGGA and TCGA databases were used to explore the possible function of TNFAIP2 in GBM. Multiplex immunohistochemistry (mIHC) staining was performed to detect the immune infiltration of tissues. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and enzyme linked immunosorbent assay (ELISA) were utilized to detect the release of damage-associated molecular patterns (DAMPs) and the activation of the immune response. A mouse glioma model was applied to examine the induction of immune response. Results: In vitro and in vivo studies demonstrated that TNFAIP2 knockdown increased the surface exposure of calreticulin (CALR), heat shock protein 70 kDa (HSP70), and heat shock protein 90 kDa (HSP90) in GBM cell lines, thereby inducing immunogenic cell death (ICD). Importantly, the study found that TNFAIP2 knockdown in combination with anti-PD-1 therapy significantly improved the overall survival of glioma in a mouse model. Conclusions: TNFAIP2 knockdown induces ICD by downregulating TNFAIP2 in GBM. In addition, TNFAIP2 knockdown sensitized glioma to anti-PD-1 therapy. Hence, targeting TNFAIP2 alone or in combination with anti-PD-1 therapy may be a potential strategy for GBM treatment through ICD. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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