BackgroundMembers of eukaryotic chaperonin family are essential for cell survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been implicated in the development of several types of cancers. However, the role of CCT3 in the development of gastric cancer has yet to be determined.MethodsThe expression patterns of CCT3 in the surgical specimens from 26 gastric cancer patients were evaluated using immunohistochemistry methods. To study the possible roles of CCT3 in the growth and survival of gastric cancer cells, RNA interference was used to knockdown CCT3 expression in gastric cancer cell lines BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation, apoptosis and in vivo growth were examined. Finally, gene expression changes related to CCT3 knockdown were studied using gene array analysis and western blotting.ResultsHigher level of CCT3 expression was detected in the gastric cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3 inhibited proliferation and colony formation while promoted apoptosis of gastric cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in nude mice when CCT3 expression was suppressed. Gene expression analysis showed that CCT3 knockdown was associated with down-regulation of mitogen-activated protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up-regulation of cyclin-dependent kinase 2 and 6.ConclusionOur results suggested that CCT3 played a critical role in gastric cancer growth and survival. Further studies on the mechanisms of CCT3 function is mandated to develop novel cancer treatment targeting CCT3.

CD8+ T cells play a central role in antitumour immunity, which often exhibit ‘exhaustion’ in the setting of malignancy and chronic viral infection due to T cell immunoglobulin and mucin domain 3 (TIM3) and myeloid‐derived suppressor cells (MDSCs). Our team previously found that overactive MDSCs and exhausted TIM3+CD8+ T cells were observed in myelodysplastic syndromes (MDS) patients. However, it is not obvious whether MDSCs suppress CD8+ T cells through TIM3/Gal‐9 pathway. Here, Gal‐9, as the ligand of TIM3, was overexpressed in MDSCs. The levels of Gal‐9 in bone marrow supernatants, serum and culture supernatants of MDSCs from MDS patients were elevated. CD8+ T cells from MDS or normal controls produced less perforin and granzyme B and exhibited increased early apoptosis after co‐culture with MDSCs from MDS. Meanwhile, the cytokines produced by CD8+ T cells could be partially restored by TIM3/Gal‐9 pathway inhibitors. Furthermore, CD8+ T cells produced less perforin and granzyme B after co‐culture with excess exogenous Gal‐9, and the function of CD8+ T cells was similarly restored by TIM3/Gal‐9 pathway inhibitors. Expression of Notch1, EOMES (associated with perforin and granzyme B secretion), p‐mTOR and p‐AKT (associated with cell proliferation) was decreased in CD8+ T cells from MDS after co‐culture with excess exogenous Gal‐9. These suggested that MDSCs might be the donor of Gal‐9, and TIM3/Gal‐9 pathway might be involved in CD8+ T cells exhaustion in MDS, and that TIM3/Gal‐9 pathway inhibitor might be the promising candidate for target therapy of MDS in the future.

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