Decreased expression of TLR7 in gastric cancer tissues and the effects of TLR7 activation on gastric cancer cells

Abstract

Abstract. The present study aimed to determine the expression of Toll-like receptor 7 (TLR7) in gastric cancer tissues and investigate the effects of its activation on gastric cancer cells. Patients with gastric cancer (n=30) and patients without gastric cancer (control; n=14) who underwent gastroscopy were enrolled in the study. Gastric cancer and cancer-adjacent tissues were obtained from the patients with gastric cancer, and normal gastric epithelial tissues were obtained from the control patients. The TLR7 mRNA and protein expressions in different tissues were investigated by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The present study also determined the effects of TLR7 activation by the agonist imiquimod on TLR7 protein expression, proinflammatory cytokine secretion and viability in SGC-7901 gastric cancer cells. The mRNA and protein expression levels of TLR7 were significantly downregulated in gastric cancer tissues compared with cancer-adjacent and normal gastric epithelial tissues (P<0.01). Imiquimod significantly increased TLR7 protein expression levels, and promoted the secretion of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 in SGC-7901 cells. Furthermore, imiquimod inhibited the proliferation of SGC-7901 cells in a dose-and time-dependent manner. Thus, the present study identified that the expression of TLR7 was decreased in gastric cancer tissues, and TLR7 activation enhanced TLR7 expression, promoted the production of proinflammatory cytokines and inhibited the growth of gastric cancer cells.

Evaluation of toll-like receptors as prognostic biomarkers in gastric cancer: high tissue TLR5 predicts a better outcome

“…TLR7 was previously thought to reduce the viability of gastric cancer cells 15 . Accordingly, we found that prognosis was better amongst patients with a high TLR7 expression in several subgroups, particularly among those with locally advanced disease.…”

“…TLR-related therapy, particularly TLR agonists, capable of activating the immune system against cancer have been broadly studied in several malignancies 18,19 . The administration of a TLR7 agonist, imiquimod, increases the expression of TLR7 in gastric cancer cells and reduces their viability 15 . Whether imiquimod has direct cytotoxic effects or if acting via the modulation of inflammatory cell activity remain incompletely understood since numerous different pathways are involved.…”

“…Subsequent TLR5 antagonism appeared to cancel the effect, suggesting that TLR5 signalling clearly contributes to the proliferation of gastric cancer cells. Yet, administering imiquimod (a TLR7 agonist) to gastric cancer cells results in a reduced proliferation 15 . In that study, TLR7 expression was low in gastric cancer cells compared to levels in adjacent healthy tissue.…”

TLRs as a Promise Target Along With Immune Checkpoint Against Gastric Cancer

“…However, another study found that GC patients with high TLR5 tissue expression can have a better prognosis, particularly who has stage II disease or intestinal-type GC (Kasurinen et al, 2019). Studies have explored that TLR7 expression is low in GC tissues, and stimulating TLR7 could promote the secretion of pro-inflammatory cytokines, and inhibit the proliferation of GC cells (Jiang et al, 2016). Thus, it can be seen that the function of different TLRs in GC is complex and different.…”

“…TLR7 is expressed on the endosomal membrane (Takeda and Akira, 2015). TLR7 was found low expressed in GC tissues (Jiang et al, 2016). Activating TLR7 can strengthen anti-cancer immunity.…”