Mapping immune cell metabolic reprogramming from mechanistic hotspots to translational directions: A bibliometric...

Immune cell metabolic reprogramming links immune function, disease microenvironments, and therapeutic responses. Although research in this field has expanded rapidly, the relationships among immune cell types, metabolic pathways, and clinical scenarios remain fragmented.

English language articles and reviews published from 2008 to 2025 were retrieved from the Web of Science Core Collection on June 14, 2025, and 3137 records were finally included. Bibliometrix, CiteSpace, VOSviewer, and related visualization tools were used for bibliometric and visual analyses. In addition, a PubMed clinical subset was established by retrieving human clinical studies published between January 1, 2008 and August 26, 2025. A total of 11 clinical studies were included.

The results showed that research on immune cell metabolic reprogramming entered a phase of rapid growth after 2016, with China and the United States as the leading contributing countries. The knowledge base of the field was mainly centered on T cell metabolic regulation, macrophage function, the tumor microenvironment, and changes in immune function. Research hotspots gradually shifted from early topics such as differentiation, activation, memory, and mTOR related immunometabolic mechanisms to the tumor microenvironment, immunosuppression, single cell analysis, efficacy evaluation, and model construction. Literature derived high frequency gene terms highlighted immune regulatory clues, including CD4, STAT3, and CD44, as well as metabolic flow related clues, including HK2, PFKFB3, LDHA, and PC. The PubMed clinical subset further showed that mitochondrial function, glycolytic changes, trained immunity, and cell therapy related metabolic states have been investigated in disease state identification, therapeutic response monitoring, and cell therapy optimization.

This study quantitatively and visually evaluated the overall development of immune cell metabolic reprogramming research. The findings suggest that the field is moving from single pathway descriptions toward a research model that integrates immune cell stratification, disease context stratification, and context specific translational investigation. By integrating the research landscape, thematic structure, molecular clues, and clinical entry points, this study provides candidate directions for independent molecular, functional, and clinical validation in immunometabolism.