| Autor: |
Chang-Woo Lee, Heounjeong Go, Su-Jin Shin, Ho Lee, Dongryeol Ryu, Baeki E. Kang, Joon-Sup Yoon, Eun-Ji Park, Jiwon Ko, Jin-Kwan Lee, Kyung-Mo Kim, Yoon Jeon, Si-Yeon Lee, Jihyun Park |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2326-6066.c.6550532 |
| Popis: |
CD8+ T cells play an important role in the elimination of tumors. However, the underlying mechanisms involved in eliciting and maintaining effector responses in CD8+ T cells remain to be elucidated. Pellino1 (Peli1) is a receptor signal-responsive ubiquitin E3 ligase, which acts as a critical mediator for innate immunity. Here, we found that the risk of developing tumors was dependent on Peli1 expression. Peli1 was upregulated in CD8+ T cells among tumor-infiltrating lymphocytes (TIL). In contrast, a deficit of Peli1 enhanced the maintenance and effector function of CD8+ TILs. The development of Peli1-deficient CD8+ TILs prevented T-cell exhaustion and retained the hyperactivated states of T cells to eliminate tumors. We also found that Peli1 directly interacted with protein kinase C-theta (PKCθ), a central kinase in T-cell receptor downstream signal transduction, but whose role in tumor immunology remains unknown. Peli1 inhibited the PKCθ pathway by lysine 48–mediated ubiquitination degradation in CD8+ TILs. In summary, the Peli1–PKCθ signaling axis is a common inhibitory mechanism that prevents antitumor CD8+ T-cell function, and thus targeting Peli1 may be a useful therapeutic strategy for improving cytotoxic T-cell activity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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