ABSTRACT
Tumors can escape immunosurveillance through immunocheckpoint such as the PD-1/PD-L1 pathway. Aikejia comes from Nocardia rubra cell-wall skeleton and can increase the number of inflammatory factors and immune cells. In this work, we showed that the levels of PD-L1 increase in CT26.WT xenograft after subcutaneous injection of Aikejia in mice, but Aikejia did not induce the expression of PD-L1 in vitro. When we treated the mice with Aikejia and blocked PD-1/PD-L1 pathway in vivo at the same time, the CT26.WT xenografts were significantly inhibited or eliminated, which was better than single treatment alone. Our results suggested that Aikejia may be an effective adjuvant for PD-1/PD-L1 immunotherapy.
ABSTRACT
BACKGROUND: Eukaryotic translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis. Changes in eIF4E activity disproportionally affect the translation of a subset of oncogenic mRNAs in some cancers. MATERIALS AND METHODS: We have assessed the expression levels of vascular endothelial growth factor C (VEGFC), eIF4E, eIF4E-binding proteins (4E-BPs) and phospho-4E-BP1 in clear cell renal carcinoma (ccRCC; n=101) using immunohistochemistry and analyzed the relevant mRNA levels and survival using online databases. RESULTS: The protein levels of VEGFC, an eIF4E-regulated gene, were upregulated in ccRCC tissues compared with adjacent normal renal tissues, indicating an enhanced eIF4E activity in ccRCC. The expression of eIF4E had no significant changes in ccRCC tissues. However, 4E-BP1 and phospho-4E-BP1 were found to be overexpressed in ccRCC tissues (P<0.05), and the high mRNA and protein levels of 4E-BP1 and phospho-4E-BP1 correlated with an unfavorable clinical outcome in ccRCC patients. Meanwhile, the mRNA expression of PIK3CD and PIK3CG were enhanced in ccRCC. CONCLUSION: From these results, we could infer that the increase in eIF4E activity may be caused by the increased phospho-4E-BP1 level, which was probably due to the activation of phosphoinositide 3-kinase (PI3K) pathway.
