Interaction between CD۱۶۱ and Vα۷.۲-Jα۳۳ in Gastric Cancer Cells with Helicobacter pylori Infection

Gastric cancer (GC) is the fifth leading cause of cancer deaths; almost one million new cases diagnosed in ۲۰۲۲ were basically restricted to Asia. One of the main factors that causes GC is Helicobacter pylori (H. pylori) infection, which causes chronic stomach inflammation and the activation of specific virulence factors. Mucosal-associated invariant T (MAIT) cells regulate the immune response against H. pylori-derived antigens in the gastric mucosa, leading to release of cytokines, such as TNF-α, IFN-γ, IL-۱۷, and IL-۹ as well as the expression of CD۳, CCR۶, and CXCR۶. Long-term exposure to H. pylori can diminish MAIT cells antitumor activity and may potentially reduce the effectiveness of cancer immunotherapies. MAIT cells express a specific subset of Vα۷.۲-Jα۳۳ TCR, which helps them identify and respond to microbial infections. Additionally, MAIT cells are the primary source of the overexpression of CD۱۶۱ (or killer cell lectin-like receptor subfamily B member ۱; KLRB۱), a C-type lectin-like receptor, which may be present on the cell surface of CD۴+/۸+/γδ T cells, natural killer (NK) cells, and NKT cells. MAIT cells expressing Vα۷.۲-Jα۳۳ and CD۱۶۱ have been found in primary and metastatic tumor cells across various types of tumors. This study investigates the co-expression of Vα۷.۲-Jα۳۳ and CD۱۶۱ in mRNA level as well as H. pylori infection status in GC patients to better understand their roles in disease progression. Methods: The study analyzed the mRNA expression profiling of Vα۷.۲-Jα۳۳ and CD۱۶۱ in ۸۶ GC tissues and adjacent normal tissues using relative real-time PCR. Results: Overexpression of CD۱۶۱ and Vα۷.۲-Jα۳۳ were indicated in ۴۴.۲% (۳۸/۸۶) and ۴۵.۳% (۳۹/۸۶) of samples, respectively. Co-expression of CD۱۶۱ and Vα۷.۲-Jα۳۳ showed a significant inverse correlation in ۸۶ GC tissues (P=۰.۰۲۱). This result can suggest that there is a regulatory correlation between CD۱۶۱ and Vα۷.۲-Jα۳۳ in the immune response to tumor cells. Further analysis indicated that dysregulation of CD۱۶۱ was significantly related to tumor size (P=۰.۰۱), grade (P=۰.۰۳), and depth of tumor invasion (P=۰.۰۳), while dysregulation of Vα۷.۲-Jα۳۳ was meaningfully associated with tumor differentiation (P=۰.۰۵) and sex of patients (P=۰.۰۴). There was a significant direct correlation between the co-expression of CD۱۶۱ and Vα۷.۲-Jα۳۳ with samples without metastasis into lymph nodes (P=۰.۰۲), primary stage I tumor progression (P=۰.۰۲), and tumor invasion to depth layers (T۲) (P=۰.۰۱). However, the results indicated a significant inverse correlation between co-expression of CD۱۶۱ and Vα۷.۲-Jα۳۳ with metastasis into lymph nodes (P=۰.۰۲), advanced stages of tumor progression (P=۰.۰۰۴), H. pylori infection (P=۰.۰۲), and grade III of differentiation (P=۰.۰۱). Conclusion: Results provides insights into the intricate relationship between MAIT cell markers and GC development. Moreover, our study underscores that the co-expression of Vα۷.۲-Jα۳۳ and CD۱۶۱ was inversely related to advanced tumor steps and H. pylori infection, suggesting an interplay in tumor progression. The findings indicate the potential of MAIT cells in shaping immune responses against GC, which could set the stage for future studies to unravel their precise functional implications in cancer immunology.

کلیدواژه ها:

Gastric cancer ، CD۱۶۱ ، Vα۷.۲-Jα۳۳ ، H. Pylori