由中国医疗保健国际交流促进会血液学分会主办，北京大学人民医院血液病研究所承办的2025北京国际造血干细胞移植学术会议于2025年4月25-26日在北京正式举办。本次会议将“移植的艺术（ART OF TRANSPLANT）”为主题，汇集全球领先的血液学专家，探索造血干细胞移植的技术创新和未来趋势，着力破解基础研究向临床应用转化的关键技术瓶颈，为血液系统疾病治疗开辟新维度。《肿瘤瞭望-血液时讯》现场特邀弗莱堡大学医学中心Lukas Michael Braun教授，阐述TIM-3阻断策略的转化价值、联合治疗策略的开发方向及未解科学问题。

《肿瘤瞭望-血液时讯》：您能解释一下免疫检查点抑制在增强抗白血病免疫中的重要性吗？目前哪些免疫检查点抑制剂在白血病研究中最有前景？

Lukas Michael Braun教授：当前，处于临床探索阶段的免疫检查点抑制剂中，以程序性死亡受体1（PD-1）、细胞毒性T淋巴细胞相关抗原4（CTLA-4）及T细胞免疫球蛋白黏蛋白3（TIM-3）最具发展潜力。从临床转化价值分析，TIM-3阻断疗法展现出独特优势。研究证实，在异基因造血干细胞移植（allo-HCT）治疗背景下，阻断PD-1或CTLA-4检查点分子与移植物抗宿主病（GVHD）风险升高存在显著相关性；然而值得注意的是，TIM-3阻断并未导致GVHD发生率上升。这一发现确使得阻断TIM-3的疗法在allo-HCT治疗体系中占据重要地位。

Oncology Frontier-Hematology Frontier：Could you explain the significance of immune checkpoint inhibition in enhancing anti-leukemia immunity?What are the most promising immune checkpoint inhibitors currently being studied for leukemia？

Professor Lukas Michael Braun：In my professional opinion, the most promising checkpoint inhibitors currently under study include the most well-known ones such as PD-1, CTLA-4, and TIM-3. From the perspective of clinical significance, TIM-3 blockade appears particularly promising. In the context of allogeneic hematopoietic stem cell transplantation (allo-HCT), blocking checkpoint molecules like PD-1 or CTLA-4 has been associated with an increased risk of graft-versus-host disease (GVHD). Notably, when TIM-3 is blocked, there is no observed elevation in GVHD incidence. Therefore, TIM-3 blockade represents a highly promising therapeutic strategy, especially in the setting of allo-HCT.

《肿瘤瞭望-血液时讯》：联合治疗是当前治疗的一个重要方向，对于免疫检查点抑制与 CAR-T 细胞疗法、靶向治疗等其他治疗方法的联合应用，您认为目前的研究取得了哪些重要成果？

Lukas Michael Braun教授：目前，关于免疫检查点抑制剂与其他疗法联合应用的临床证据仍较为有限，但临床前研究提供了重要启示。研究表明，特定配体分子的表达水平是决定阻断TIM-3疗效的核心生物标志物。例如，靶向这些差异性配体的新型抑制剂开发，可能形成协同增强移植物抗白血病（GVL）效应的联合治疗方案。基于现有证据，将免疫检查点抑制剂整合至allo-HCT治疗体系，或将成为目前最具突破潜力的免疫治疗模式。

Oncology Frontier-Hematology Frontier：Combination therapy is a key direction in current therapy. What important progress do you think has been made in combining immune checkpoint inhibition with other therapies like CAR-T cell therapy and targeted therapy? 
 

Professor Lukas Michael Braun：To date, there is limited clinical evidence supporting combination therapies involving immune checkpoint inhibitors and other treatments. However, preclinical research offers substantial insights. Our studies have demonstrated that the expression of specific ligands is critical for the efficacy of TIM-3 blockade. For instance, identifying additional molecules capable of blocking these distinct ligands may represent a viable combination strategy to enhance graft-versus-leukemia (GVL) activity synergistically. Additionally, integrating checkpoint inhibitors with allo-HCT maybe the most potent form of immunotherapy we have—already constitutes a highly promising approach.

《肿瘤瞭望-血液时讯》:展望未来，您认为免疫检查点抑制剂在白血病治疗中最具转化潜力的方向是什么？

Lukas Michael Braun教授：免疫检查点抑制剂与异基因造血干细胞移植的联合治疗方案在拓展适应症边界及降低移植后复发率方面展现出显著潜力。然而，目前仍存在诸多亟待明确的科学问题，包括需精准识别对此类疗法产生应答的白血病亚型。临床前研究数据显示，不同免疫检查点配体的表达水平具有关键调控作用。现阶段亟需开展临床研究以系统验证三大核心问题：其一，明确获得治疗应答的患者群体特征；其二，界定可受益的白血病具体分型；其三，解析治疗反应性与驱动基因突变间的相关性。研究的终极目标在于建立治疗前预测模型，实现应答者与非应答者的精准区分。

Oncology Frontier-Hematology Frontier：Looking ahead, what do you see as the most transformative direction for immune checkpoint inhibitors in leukemia?

Professor Lukas Michael Braun：I think combining immune checkpoint inhibitors with allo-HCT shows promise in expanding the boundaries of allo-HCT and lowering relapse rates post - stem cell transplantation. However, there's still much to learn, such as identifying the specific types of leukemia that respond to these therapies. Our preclinical studies indicate that the expression of different ligands is crucial. Now, clinical studies are needed to confirm which patients respond to these therapies, the types of leukemia that can be treated, and whether responses depend on driver mutations. The goal is to be able to differentiate between responders and non - responders before treatment initiation.

Lukas Michael Braun

弗莱堡大学医学中心（Freiburg University Medical Center）

博士后科学家丨癌症免疫学丨免疫疗法（Postdoctoral Scientist | Cancer immunology | Immunotherapy）