Dynamic change of circulating innate and adaptive lymphocytes subtypes during a cascade of gastric lesions

Abstract

According to the Correa model, the intestinal‐type gastric cancer (GC) is preceded by premalignant lesions, including chronic gastritis, intestinal metaplasia and dysplasia. However, the dynamic change of innate and adaptive immune response during this process has not been studied comprehensively. In this study, we performed a comprehensive and trajectory analysis of circulating innate lymphoid cells (ILCs) and adaptive Th lymphocytes subtypes in patients spanning a cascade of gastric lesions. Increased circulating ILC2s frequency was found in the gastritis, premalignant stage and GC group, whereas further decreased ILC2s were detected in the GC group compared with the premalignant group. Moreover, ILC3s level was higher in both gastritis, premalignant lesion and GC stage, compared with healthy controls. Furthermore, up‐regulated T follicular helper (Tfh) cell proportions were detected in the gastritis and premalignant process. In conclusion, by analyzing the circulating ILCs and Th cells frequency and the key cytokine production or immunoglobulin level, we demonstrated the potential involvement of ILC3 and Tfh in the gastric diseases. These findings will help to understand the immunologic mechanisms in both GC and the premalignant process and contribute to serve potential therapeutic targets to prevent the GC development.

Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis

“…Flow cytometry was performed using a FACSCanto instrument (BD Biosciences, San Jose, CA, USA) and analyzed using FlowJo software 10.8.1. The cell type annotation and gating strategy were performed as shown previously (27)(28)(29).…”

“…Individual immunity is coordinated across tissues, and the colonic antitumor immune response depends on continuous communication with the peripheral blood (25,26). Our previous study demonstrated peripheral adaptive and innate lymphocyte changes during human gastric cancer development (27). Considering the easily obtainable and non-invasive characteristics of peripheral blood samples, exploring changes in peripheral immune profiles is crucial and may help discover key functional cell subpopulations during CRC carcinogenesis.…”

The Roles of Innate Lymphoid Cells in the Gastric Mucosal Immunology and Oncogenesis of Gastric Cancer

“…However, the role of ILC3s in gastric cancer is not well understood. Studies have shown that the levels of ILC3s and IL-22 in patients with gastritis, precancerous lesions, and gastric cancer are significantly higher than those in healthy populations, suggesting that ILC3s may play a role in gastric oncogenesis and have important immune functions [ 150 ]. Nevertheless, further high-quality studies are needed to deeply reveal and understand the relationship between ILC3s and gastric oncogenesis, especially regarding molecular mechanisms.…”

“…Elevated ILC3 and IL-22 levels in gastritis and gastric cancer patients (specific roles uncertain) [ 150 ]…”

Fuzheng Nizeng Decoction regulated ferroptosis and endoplasmic reticulum stress in the treatment of gastric precancerous lesions: A mechanistic study based on metabolomics coupled with transcriptomics

“…According to the Correa model, the malignant development of normal gastric mucosa into gastric cancer is a long-term stage, especially in the three stages of “chronic atrophic gastritis - intestinal metaplasia - intraepithelial neoplasia” ( Correa, 1988 ). Therefore, three stages are termed gastric precancerous lesions (GPL), which are well-known risk factors for the development of intestinal-type gastric adenocarcinomas ( Fu et al, 2022 ). However, at present, there is no effective medicine for GPL treatment in modern medicine.…”