免疫治疗，特别是免疫检查点阻断（ICB），在癌症治疗方面已经显示出巨大的潜力，并成为对已经耗竭了传统治疗方案的患者带来希望的灯塔。尽管ICB已获准用于治疗先进肿瘤，但其疗效仍然仅限于小部分患者。作为一种系统性疾病，癌症可以引起系统性免疫系统组成和功能的改变，并且ICB耐药性通常涉及肿瘤微环境（TME）和系统性免疫宏环境之间的对话。虽然对肿瘤进展和ICB耐药性的调查主要集中在TME本身上，但系统性免疫系统和免疫宏环境的变化仍然不十分清楚。由于脾脏是最大的二级淋巴器官，对脾脏的研究和讨论可能提供有关系统性免疫状态和TME组分的有价值的见解。最近的研究强调了脾脏在肿瘤进展和免疫疗法中的重要性，特别是在红细胞祖细胞（EPC）这一显著的细胞亚群的背景下。在本综述中，我们讨论了脾外骨髓造血（EMH）作为肿瘤宿主相互作用中介的机制和作用，并探讨了EPC-TME勾结的机制。我们进一步总结了EPC靶向策略的进展，并强调研究EPC在肿瘤进展和治疗中的作用和机制的潜力，这可能具有深远的影响。版权所有©2023。Elsevier B.V.出版。

Immunotherapy, particularly immune checkpoint blockade (ICB), has shown great promise in the treatment of cancer and emerged as a beacon of hope for patients who have exhausted traditional therapeutic options. Despite ICB's approval for the treatment of advanced tumors, its efficacy remains limited to a small subset of patients. As a systemic disease, cancer can induce changes in the composition and function of the systemic immune system, and ICB resistance often involves a dialogue between the tumor microenvironment (TME) and the systemic immune macroenvironment. While investigations into tumor progression and ICB resistance have largely focused on the TME itself, the alterations in the systemic immune system and immune macroenvironment are still poorly understood. Given the spleen's role as the largest secondary lymphoid organ, its examination and discussion may provide valuable insights into the systemic immune status and TME components. Recent studies have highlighted the importance of the spleen in tumor progression and immunotherapy, particularly in the context of erythroid progenitor cells (EPCs), a significant cell subpopulation. In this review, we discuss the mechanisms and role of splenic extramedullary hematopoiesis (EMH) as an intermediary in tumor-host interactions and explore the mechanism of EPC-TME collusions. We further summarize the progress in EPC-targeting strategies and emphasize the potential for further research into the role and mechanisms of EPCs in tumor progression and treatment, which could have far-reaching implications.Copyright © 2023. Published by Elsevier B.V.