Tristetraprolin Overexpression in Gastric Cancer Cells Suppresses PD-L1 Expression and Inhibits Tumor Progression by Enhancing Antitumor Immunity

Jian Guo; Huiheng Qu; Ting Shan; Yigang Chen; Ye Chen; Jiazeng Xia

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자료유형: 학술저널

저자정보: Jian Guo (Nanjing Medical University) Huiheng Qu (Nanjing Medical University) Ting Shan (Nanjing Medical University) Yigang Chen (Nanjing Medical University) Ye Chen (Nanjing Medical University) Jiazeng Xia (Nanjing Medical University)

저널정보: 한국분자세포생물학회 Molecules and Cells Molecules and Cells 제41권 제7호

발행연도: 2018.7

수록면: 653 - 664 (12page)

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The RNA-binding protein tristetraprolin (TTP) binds to adenosine- uridine AU-rich elements in the 3’-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their microenvironment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PDL1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

#immunity #PD-L1 #Tregs #tristetraprolin #tumor progression

참고문헌 (46)

참고문헌 신청

Ai, R. / 2017 / Microenvironmental regulation of the progression of oral potentially malignant disorders towards malignancy / Oncotarget 8:81617~81635

Becht, E. / 2016 / Cancer immune contexture and immunotherapy / Curr. Opin. Immunol. 39:7~13

Brooks, S.A. / 2013 / Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action / Biochim. Biophys. Acta 1829:666~679

Cho, J. / 2017 / Programmed cell deathligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability / Oncotarget 8:13320~13328

Curiel, T.J. / 2004 / Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival / Nat. Med. 10:942~949

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