Editor’s Note: From June 6–8, 2025, the “2025 International Symposium on Clinical and Translational Hematology and the 10th Two Rivers Forum on Hematologic Malignancies” was held in Chongqing, China. The conference was hosted by the Chinese Medical Journal Publishing Company (Chinese Medical Association Journal Office) and Chinese Medical Journal (English Edition), and organized by the Hematology Center of Xinqiao Hospital, Army Medical University. The conference was chaired by Professors Xiaojun Huang, Jianxiang Wang, Depei Wu, and Yu Hu, with Professors Xi Zhang and Defu Zeng from the Beckman Research Institute at City of Hope serving as executive chairs.Leading international experts were invited to share cutting-edge research and clinical advances in hematology. At the conference, Oncology Frontier – Hematology Frontier had the privilege of interviewing Prof. Defu Zeng, who provided a detailed explanation of one of his most significant studies, focusing on the cellular and molecular mechanisms of chronic graft-versus-host disease (cGVHD) and its therapeutic progress.Oncology Frontier-Hematology Frontier：In your research, what new cellular and molecular mechanisms of chronic graft-versus-host disease (cGVHD) have been identified? Compared with previous understandings, what major breakthroughs do these new findings represent?
Prof. Defu Zeng： Graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation. It occurs when donor immune cells attack the recipient’s tissues. GVHD is typically classified into acute and chronic forms, with chronic GVHD often emerging as a progression or consequence of the acute phase.
In our recent studies, we’ve characterized cGVHD as involving two key transitions: first, the shift from acute GVHD to chronic GVHD, and second, the progression within chronic GVHD from an inflammatory stage to a fibrotic stage.
During acute GVHD, donor-derived alloreactive T helper 1 (TH1) cells become activated and secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). This cytokine activates macrophages, which then mediate tissue inflammation. If this acute inflammatory phase is not resolved, the disease progresses to chronic GVHD.
As the tissue attempts to heal, a subset of TH1 and Th2-like T cells expands. These cells activate macrophages that produce transforming growth factor-beta (TGF-β), which in turn stimulates fibroblasts to produce collagen. Collagen production is normally part of the repair process, but in cGVHD this mechanism becomes dysregulated, leading to excessive collagen deposition and tissue fibrosis.
What’s critical here is that fibrosis in cGVHD is not merely a late-stage consequence, but an active process driven by ongoing immune dysregulation. Understanding this has important clinical implications. Effective management of chronic GVHD requires identification of the disease stage—whether it’s predominantly inflammatory or fibrotic—so that appropriate stage-specific therapies can be implemented.
Oncology Frontier-Hematology Frontier：In your view, how will this conference promote academic exchanges and cooperation in the field of hematology between China, the United States, and globally?
Prof. Defu Zeng： International conferences like this one play a vital role in fostering collaboration between scientists across borders. They offer a valuable opportunity for physician-scientists from the United States, China, and other countries to engage in direct dialogue, exchange data, and discuss therapeutic innovations. These kinds of interactions not only generate new research ideas but also accelerate the development of more effective treatments through global cooperation. Thank you.
Conclusion
Prof. Defu Zeng’s research offers new insights into the dynamic immune-to-fibrotic transition in chronic skin GVHD, providing a comprehensive mechanistic understanding of how TH1/TH2-driven inflammation evolves into tissue fibrosis. His findings deepen the scientific understanding of disease progression and lay a clear theoretical foundation for stage-specific treatment strategies.
Importantly, Prof. Zeng emphasized the value of international academic exchange, highlighting global collaboration as a driving force in advancing the field of transplant immunology. As the discipline moves toward individualized therapies, such mechanistic discoveries and cross-border partnerships will play a decisive role in improving patient outcomes.
Expert Profile
Prof. Defu Zeng Professor, Beckman Research Institute, City of Hope, USA Former Member (2014–2018), NIH Transplantation Tolerance and Tumor Immunology Study Section; Special Reviewer, NIH
Research Focus: Prof. Zeng specializes in the mechanisms, prevention, and treatment of graft-versus-host disease (GVHD), and studies the regulatory interactions between PD-1 and PD-1/CD80 in modulating GVHD and graft-versus-leukemia (GVL) effects.
