Abstract
Gastric cancer (GC) is one of the most common cancers in the world, and the incidence of gastric cancer in Asia appears to increase in recent years. Although there is a lot of improvement in treatment approaches, the prognosis of GC is poor. So it is urgent to search for a novel and more effective treatment to improve the survival rate of patients. Both innate immunity and adaptive immunity are important in cancer. In the innate immune system, pattern recognition receptors (PRRs) activate immune responses by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs). Many studies have reported that TLRs are involved in the occurrence, development, and treatment of GC. Therefore, TLRs are potential targets for immunotherapy to gastric cancer. However, gastric cancer is a heterogeneous disorder, and TLRs function in GC is complex. TLRs agonists can be potentially used not only as therapeutic agents to treat gastric cancer but also as adjuvants in conjunction with other immunotherapies. They might provide a promising new target for GC treatment. In the review, we sort out the mechanism of TLRs involved in tumor immunity and summarize the current progress in TLRs-based therapeutic approaches and other immunotherapies in the treatment of GC.
Highlights
Gastric cancer (GC), is the second leading cause of cancer death worldwide according to the latest WHO statistics in 2018 (Bray et al, 2018)
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)
Wu et al found that lipo-OVA (Ovalbumin fused with the TLR2 agonist, the lipid part of the bacteria) showed a strong anti-tumor effect by activating bone marrow-derived-dendritic cells (BMDCs) maturation, promoting cross-presentation of tumor antigen, inducing cytotoxic T lymphocytes (CTLs) responses, increasing the numbers of CD8+ T cells (Wu et al, 2016)
Summary
Gastric cancer (GC), is the second leading cause of cancer death worldwide according to the latest WHO statistics in 2018 (Bray et al, 2018). Gastric cancer can be removed by EMR (endoscopic mucosal resection) or ESD (endoscopic submucosal dissection), the longterm prognosis is good at present (Ko et al, 2016). What makes GC difficult to treat is due to the patients with GC usually without any early symptoms. There are several standard treatments to treat advanced gastric cancer: surgical resection, chemotherapy, radiotherapy, chemoradiation, and targeted therapy. The 5-year survival rate of patients with GC had no significant improvement. The patients had some side effects during and after treatment, including nausea, vomiting, reflux, malnutrition, etc. The quality of life of the patients decreased significantly. This makes people with gastric cancer suffer both physically and mentally
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