Research Progress and Future Directions in Immune Cell Crosstalk in the Esophageal Cancer: A Bibliometric Analysis

The complexity of immune cell crosstalk plays a key role in immunotherapy resistance for esophageal cancer, while systematically bibliometric analysis in this field to describe knowledge structure, hotspots and identify future research trends remains lacking.

We retrieved publications on immune cell crosstalk in esophageal cancer from the Web of Science Core Collection, covering 2007 to 2025. A total of 510 articles and reviews were analyzed with CiteSpace and VOSviewer to assess publication trends, collaborative networks, keyword co‑occurrence, citation bursts, and research hotspots.

Research output has grown sharply since 2020. China, the United States, and Japan are the top three countries by productivity. Keyword analysis showed a progression from basic mechanisms such as apoptosis and the NF-κB pathway toward immunotherapy combinations, tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs). Crosstalk networks involving T cells and macrophages are now relatively well understood, whereas interactions between regulatory T cells (Tregs) and natural killer cells (NK cells) remain poorly defined. In addition, most studies have focused on chemo-immunotherapy, leaving the cellular crosstalk under radiotherapy-based treatments largely unstudied.

Our findings suggest that future research may benefit from prioritizing the study of Tregs and NK cells crosstalk in patients receiving radiotherapy-based treatments, and from examining their interactions with other cells, particularly TAMs and CAFs.