In March, as spring brings renewed vitality to Beijing, the 9th Beijing Conference on Thrombosis and Hemostasis, together with the 7th Beijing Hematologic Oncology and Immunology Summit Forum, was held from March 27 to 28, 2026. Centered on advances in the diagnosis and treatment of thrombotic and hemostatic disorders, as well as hematologic malignancies and immunology, the meeting highlighted cutting-edge developments and evolving clinical strategies. During the conference, Oncology Frontier – Hematology Frontier invited Professor Zonghong Shao from Tianjin Medical University General Hospital to deliver an in-depth presentation on immune abnormalities in patients with myelodysplastic syndromes (MDS) and corresponding therapeutic strategies. Professor Shao systematically analyzed the core features of immune dysregulation in MDS, outlined principles for immune function assessment, clarified the indications and risk considerations for immunosuppressive therapy, and shared forward-looking perspectives on immunotherapy and individualized treatment approaches.
Mechanisms of Immune Dysregulation and Clinical Evaluation in MDS
Oncology Frontier – Hematology Frontier: The pathogenesis of MDS is closely associated with immune dysregulation. What are the latest insights into the core mechanisms underlying immune abnormalities in MDS, and how should clinicians evaluate disease status and prognosis using immunological indicators?
Professor Zonghong Shao: The mechanisms of immune dysregulation in MDS can be understood from three key aspects. First, immune abnormalities are secondary events arising from malignant and MDS-related clonal hematopoiesis; in other words, immune dysregulation itself is not the primary driver but rather a consequence of clonal evolution. Second, these immune abnormalities exert inflammatory damage on normal hematopoiesis, impairing its recovery and further suppressing normal blood cell production, ultimately leading to ineffective hematopoiesis. Third, the immune system exhibits excessive tolerance toward the MDS clone, resulting in an inability to effectively eliminate or control its proliferation, thereby facilitating disease progression toward leukemia. These three features collectively define the fundamental characteristics of immune and inflammatory dysregulation in MDS.
A rigorous evaluation of cellular immune function in patients with MDS requires comparison not only with healthy individuals but also with patients who have cytopenias arising from non-MDS causes. Such comparisons reveal that antitumor immunity in MDS is relatively insufficient rather than absolutely enhanced. Importantly, immune competence should not be assessed solely on the basis of absolute numerical values. Instead, it must be interpreted in the context of the physiological task the immune system is expected to perform—namely, the elimination of the MDS clone.
In healthy individuals, MDS clones are virtually absent, and therefore their immune systems are not subjected to a comparable burden. In contrast, even when certain immune parameters in MDS patients appear elevated relative to normal controls, they remain inadequate when considered against the substantial clonal load that must be controlled. As an analogy, a person who has been fasting for ten days may consume more food per meal than someone who has not been fasting, yet that intake may still be insufficient relative to their physiological needs. Similarly, the adequacy of antitumor immunity in MDS should be judged by its capacity to match the demands imposed by the clonal burden, rather than by simple comparison with normal reference values.
Principles and Clinical Application of Immunosuppressive Therapy
Oncology Frontier – Hematology Frontier: Immunosuppressive therapy represents an important treatment option for selected patients with MDS. In clinical practice, what key principles guide patient selection, timing, and therapeutic strategies, and how should clinicians balance efficacy against risks such as infection?
Professor Zonghong Shao: In the context of MDS, I advocate two principal strategies for immunomodulatory intervention. The first involves selectively targeting inflammatory factors that suppress normal hematopoiesis. For example, agents such as luspatercept can block relevant pathways, thereby relieving inhibitory effects on normal blood cell production and facilitating hematopoietic recovery.
The second strategy emphasizes immune intervention after reducing the burden of malignant clones. This can be achieved through approaches such as hypomethylating agents, CAR-T therapy, chemotherapy, or hematopoietic stem cell transplantation. Once the clonal burden has been effectively reduced, targeted modulation of immune and inflammatory responses can be implemented.
By contrast, administering immunosuppressive therapy in the absence of adequate control of the malignant clone may be counterproductive. Although such an approach may transiently alleviate inflammatory suppression of normal hematopoiesis, it can further exacerbate immune tolerance toward the malignant clone, facilitating immune escape, rapid clonal expansion, and eventual leukemic transformation. In this setting, the risks outweigh the benefits.
It is also important to recognize that some patients who respond completely to immunosuppressive therapy and achieve sustained normalization of blood counts may not have true MDS. In such cases, dysplastic hematopoiesis may be attributable to inflammatory conditions, autoimmune disorders, or infections rather than a malignant clone. If no clonal abnormality is ever detected and remission is sustained, these patients should be reclassified to avoid misdiagnosis and to ensure the integrity of clinical data.
Future Directions in MDS Immunotherapy and Individualized Treatment
Oncology Frontier – Hematology Frontier: With the rapid development of targeted therapies and immunotherapy, novel strategies addressing immune dysregulation in MDS are continually emerging. How do you envision the future direction of MDS immunotherapy, and what recommendations would you offer clinicians regarding individualized treatment?
Professor Zonghong Shao: Further improvement in MDS outcomes, including through immunotherapeutic approaches, depends on progress in three critical areas.
First, diagnostic precision must be strengthened. Misdiagnosis, underdiagnosis, and the misclassification of pseudo-MDS as true MDS—or vice versa—remain significant challenges. Accurate diagnosis requires integration of clonal hematopoiesis, morphological dysplasia, and therapeutic response. Given the complexity of MDS, retrospective reassessment based on treatment outcomes can also help refine diagnostic accuracy and ensure the reliability of clinical research.
Second, treatment strategies must be optimized with a primary focus on clonal hematopoiesis, which represents the central pathological process in MDS. Current approaches, such as hypomethylating agents, have laid the foundation, but future advances will likely depend on the identification of disease-specific targets. This may enable the development of highly precise therapies, including targeted inhibitors, pathway-directed agents, and cellular therapies such as CAR-T. Should shared antigens be identified, antibody-based strategies targeting common clonal features could offer highly efficient and safe treatment options.
Third, immunotherapy should be further refined to enhance antitumor immunity. Even if some degree of damage to normal hematopoiesis occurs, this may be an acceptable trade-off if effective eradication of the malignant clone can be achieved. Once the clonal burden has been significantly reduced, normal hematopoiesis has the capacity to recover. At that stage, carefully timed anti-inflammatory interventions may help accelerate and improve hematopoietic restoration. However, such interventions should be introduced only after adequate control of the malignant clone, as premature use may be detrimental.
In summary, through precise diagnosis, effective targeting of clonal hematopoiesis, and the rational integration of immune and anti-inflammatory strategies, meaningful improvements in the treatment outcomes of MDS can be achieved in the years ahead.
Expert Profile
Zonghong Shao, MD, PhD Second-Level Professor, Chief Physician, Doctoral Supervisor
Professor Shao is a leading authority in hematology. He previously served as President of the Second Affiliated Hospital of Tianjin Medical University, Director of the Department of Internal Medicine and Hematology at Tianjin Medical University General Hospital, and Deputy Director of the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College.
He has also held key academic positions, including Associate Editor-in-Chief of the Chinese Journal of Hematology, Vice Chair of the Hematology Branch of the Chinese Medical Association (8th–10th terms), Vice President of the Hematology Branch of the Chinese Medical Doctor Association, Chair of the Hematology Immunology Branch of the Chinese Society of Immunology, and Chair of the Clinical Flow Cytometry Group. He currently serves as President of the Hematology Branch of the Tianjin Medical Doctor Association.
