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

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.

Pattern recognition receptors in health and diseases

“… 444 Clinically, PRR agonists can be potentially used not only as therapeutic agents to treat but also as adjuvants in conjunction with other immunotherapies. 445 , 446 Due to the instability and drug resistance of existing drugs, some adjuvants targeting PRRs emerge as the times require. A TLR3-specific adjuvant, ARNAX, can enhance DC priming and CTL proliferation without cytokine toxicity.…”

Spherical Nucleic Acids as Precision Therapeutics for the Treatment of Cancer—From Bench to Bedside

“…TLR7 and TLR8 are activated by guanosine (G)- and uridine (U)-rich single-stranded oligoribonucleotides. TLR9 senses single-stranded oligodeoxynucleotides that contain repeating unmethylated cytosine-guanosine (CpG) sequences, and TLR3 binds to ∼40–50 base pairs (bp) of non-sequence-specific double-stranded RNA (dsRNA) [ 53 , 54 , 55 ]. SNAs represent ideal and attractive modalities for activating endosomal TLRs, as SNAs undergo SR-A-dependent endocytosis and are enriched within the endosomal compartment.…”

Interdisciplinary insights into the link between gut microbiome and gastric carcinogenesis—what is currently known?

“…In addition, what is worth to mention, SNPs seem to be strongly ethnic-related [ 43 , 46 ]. The importance of TLRs in the development, as well as in the treatment of GC, can be proven by data suggesting that TLRs can be promising targets in immunotherapy of gastric cancer [ 46 , 47 ]. Apart from the TLRs polymorphisms, other elements of innate immunity can increase the risk of GC, such as specific SNPs of CD14 gene which participate in the immune response together with TLR-4 [ 46 , 48 ] and specific variants of NODs [ 46 ].…”