Can the Analysis of Toll-like Receptors (TLR) on NK and NKT-like Cells Improve Gastric Cancer Diagnostics and Treatment?

Abstract

Background/Objectives: The aim of this study was to determine the assessment of the percentage of NK and NKT-like cells expressing Toll-like receptors (TLR-2, TLR-3, TLR-4, and TLR-9) in patients with gastric cancer (GC) compared with healthy volunteers (HV) and to investigate differences according to cancer subtype. We also assessed TLR gene expression by RT-qPCR to assess whether TLRs could be diagnostic and prognostic biomarkers. Methods: The study included 86 patients with histologically confirmed gastric cancer and 30 healthy volunteers. Peripheral blood samples were collected from the participants, and TLR expression on NK and NKT-like cells was assessed by flow cytometry and RT-qPCR. The expression of TLR2, TLR3, TLR4, and TLR9 genes was assessed using genetic material derived from NK and NKT-like cells sourced from PBMC. The obtained results were statistically analyzed using Mann-Whitney U and Kruskal-Wallis tests, and the predictive ability of variables was assessed using ROC curve analysis. Results: A significantly higher expression of TLR receptors (TLR-2, TLR-3, TLR-4, and TLR-9) was found in patients with gastric cancer compared to healthy volunteers (p < 0.05). TLR expression also differed depending on the cancer subtype, and higher expression was observed in more advanced GC subtypes. RT-qPCR analysis showed significantly increased expression of TLR genes in the group of GC patients. ROC curves indicate a high ability of TLRs to differentiate between GC patients and healthy individuals. Conclusions: The expression of TLRs on NK and NKT-like cells is clearly increased in patients with gastric cancer, especially in more advanced subtypes of the tumor. The results suggest that TLRs could potentially be used as diagnostic and prognostic biomarkers and represent potential targets for immune therapies in GC. However, further studies are needed to determine the functional role of TLRs in disease progression and the possibility of their use in personalized treatment.