CCL19/CCR7 drives regulatory T cell migration and indicates poor prognosis in gastric cancer

• Published in: BMC cancer Vol. 23; no. 1; p. 464
• Main Authors: Xu, Danhua, Liu, Xu, Ke, Shouyu, Guo, Yixian, Zhu, Chunchao, Cao, Hui
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19.05.2023; BioMed Central; BMC
• Subjects: Analysis; Antibodies; Apoptosis; Bioinformatics; Cancer; Cancer therapies; Care and treatment; CCL19; CCL19 protein; CCR7; CCR7 protein; CD8 antigen; CD8 + T cells; Cell adhesion & migration; Cell death; Cell migration; Chemokine CCL19; Chemokines; Chemotherapy; Clinical trials; Comparative analysis; Correlation analysis; Diagnosis; Flow cytometry; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gastric cancer; Gene expression; Genomes; Health aspects; Humans; Immune checkpoint inhibitors; Immunotherapy; Lymphocytes; Lymphocytes T; Medical colleges; Medical prognosis; Morbidity; Mortality; Patient outcomes; Patients; PD-1 protein; Prognosis; Receptors, CCR7 - genetics; Receptors, CCR7 - metabolism; Software; Statistical analysis; Stomach cancer; Stomach Neoplasms - pathology; T cells; T-Lymphocytes, Regulatory; Therapeutic targets; Treg cells; China; United States > US; Treg cells; CCR7; CCL19; CD8 + T cells; Gastric cancer; Chemokines
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-10882-7

Gastric cancer is associated with significant morbidity and mortality in the world. Blocking programmed cell death protein 1 pathway have been approved for the treatment of a variety of tumors and have achieved remarkable clinical therapeutic effects. However, immune checkpoint inhibitors failed to achieve satisfactory results in gastric cancer. There is a need to identify novel immunotherapy targets in gastric cancer. We analysed the correlation between Treg cells and CD8 + T cells in gastric cancer samples. We studied the relationship between chemokines and Treg cells or CD8 + T cells in gastric cancer. We compared CCL19/CCR7 expression in gastric cancer patients in TCGA database. We performed transwell experiments to determine the influence of CCL19 on Treg cells and CD8 + T cells migratory capacity. We conducted survival analysis of CCL19 and CCR7 in gastric cancer database. Treg cells show positive correlation with CD8 + T cells in gastric cancer. Treg cell expression was significantly upregulated in tumor tissues. Patients with high FOXP3 expression had worse overall survival than those with low FOXP3 expression. CCL19 had strong correlation with FOXP3 and weak correlation with CD8A. CCL19 had strong impact on the migratory capacity of Treg cells but weak impact on the migratory capacity of CD8 + T cells. Both CCL19 and CCR7 expression were significantly upregulated in gastric cancer tissues. Survival analysis demonstrated that both CCL19 and CCR7 indicate poor prognosis in gastric cancer. CCL19/CCR7 may be a potential novel therapeutic target in gastric cancer.