expression-clinical-significance-role-immunotherapy-efficacy

Expression, Clinical Significance, and Role in Immunotherapy Efficacy Evaluation of the Co-stimulatory Molecule LLT1 in Gastric Cancer

LLT1 is a novel immune checkpoint molecule and potential therapeutic target. Immunotherapy has improved outcomes in advanced gastric cancer; however, many ...

The First Affiliated Hospital of Soochow University

Gastric cancer (GC) is one of the most prevalent types of cancer worldwide. B7-H3, an immune checkpoint molecule with promising potential, has been found to be overexpressed in various cancers. CD47 is an anti-phagocytic molecule that interacts with the signal regulatory protein alpha (SIRPα) to affect phagocytes. The relationship between the expression of B7-H3 and CD47, two potential therapeutic targets found in tumor cells, remains unknown. In this study, our objective is to investigate the clinical significance of co-expression of B7-H3 and CD47, as well as the potential therapeutic value of combination therapy in GC.

B7-H3 and CD47 co-expression in gastric cancer is a predictor of poor prognosis and potential targets for future dual-targeting immunotherapy.

The vascular system is a vital circulatory network in the human body that plays a critical role in almost all physiological processes. The production of blood vessels in the body is a significant area of interest for researchers seeking to improve their understanding of vascular function and maintain normal vascular operation. However, an excessive or insufficient vascular regeneration process may lead to the development of various ailments such as cancer, eye diseases, and ischemic diseases. Recent preclinical and clinical studies have revealed new molecular targets and principles that may enhance the therapeutic effect of anti-angiogenic strategies. A thorough comprehension of the mechanism responsible for the abnormal vascular growth in disease processes can enable researchers to better target and effectively suppress or treat the disease. N-methyladenosine (mA), a common RNA methylation modification method, has emerged as a crucial regulator of various diseases by modulating vascular development. In this review, we will cover how mA regulates various vascular-related diseases, such as cancer, ocular diseases, neurological diseases, ischemic diseases, emphasizing the mechanism of mA methylation regulators on angiogenesis during pathological process.

The N-methyladenosine modification in pathologic angiogenesis.

IntroductionGastric cancer (GC) is a highly heterogeneous malignancy, necessitating novel therapeutic targets. B7-H3 and CD39, as immune checkpoints, are potential modulators of the tumor microenvironment and may influence the efficacy of immunotherapies.MethodsB7-H3, CD39, and CD8 expression was assessed via immunohistochemistry (IHC) in 268 GC tissues and 80 gastric precancerous lesions. The correlation between B7-H3 and CD39 expression was analyzed using Spearman's correlation. Multiplex immunohistochemistry (m-IHC) was employed to determine the co-localization of B7-H3 and CD39 in GC tissues. Kaplan-Meier survival analysis and Cox regression models were utilized to evaluate clinical outcomes in different patient subgroups.ResultsBoth B7-H3 and CD39 expression showed a stepwise increase during gastric carcinogenesis including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) to GC, with significantly higher expression levels in GC tissues compared to all precancerous lesions ( < .05). A significant positive correlation was observed between B7-H3 and CD39 expression (r = 0.2398,  < .001). Co-localization of B7-H3 and CD39 was detected within tumor nests and peritumoral regions and was significantly correlated with tumor volume ( = .017), tumor stage ( = .001), tumor depth ( = .002), lymph node metastasis ( = .005), lymph node involvement ( = .004) and distant metastasis ( = .028). Kaplan-Meier analysis revealed that patients with co-localized B7-H3 and CD39 expression exhibited significantly poorer prognosis ( = .0055). Cox regression analysis confirmed that this co-localization was a significant predictor of survival ( = .007) and an independent prognostic factor in multivariate analysis ( = .027).ConclusionThe co-localized expression of B7-H3 and CD39 in GC patients is strongly associated with poor prognosis. This dual-target expression pattern provides novel insights and a theoretical foundation for the development of dual-target immune checkpoint inhibitors as potential therapeutic strategies.

Article	Year
B7-H3 and CD47 co-expression in gastric cancer is a predictor of poor prognosis and potential targets for future dual-targeting immunotherapy. Journal of cancer research and clinical oncology\| PubMed ID: 37715830	2023
The N-methyladenosine modification in pathologic angiogenesis. Life sciences\| PubMed ID: 38244915	2024
B7-H3 and CD39 Co-Localization in Gastric Cancer: A Potential Prognostic Biomarker and Potential Dual-Target for Immunotherapy. Technology in cancer research & treatment\| PubMed ID: 40990627	2025

Hanqin Xuan

Biography

JoVE Journal Publications

Other Publications