文章：

MDSC检查点阻断疗法：克服癌症免疫治疗中免疫抑制的新突破点

MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy

原文发布日期：2025-03-26 

英文摘要：

Despite the success of cancer immunotherapy in treating hematologic malignancies, their efficacy in solid tumors remains limited due to the immunosuppressive tumor microenvironment (TME), which is mainly formed by myeloid-derived suppressor cells (MDSCs). MDSCs not only exert potent immunosuppressive effects that hinder the success of immune checkpoint inhibitors (ICIs) and adaptive cellular therapies, but they also promote tumor advancement through non-immunological pathways, including promoting angiogenesis, driving epithelial-mesenchymal transition (EMT), and contributing to the establishment of pre-metastatic environments. While targeting MDSCs alone or in combination with conventional therapies has shown limited success, emerging evidence suggests that MDSC checkpoint blockade in combination with other immunotherapies holds great promise in overcoming both immunological and non-immunological barriers. In this review, we discussed the dual roles of MDSCs, with a particular emphasis on their underexplored checkpoints blockade strategies. We discussed the rationale behind combination strategies, their potential advantages in overcoming MDSC-mediated immunosuppression, and the challenges associated with their development. Additionally, we highlight future research directions aimed at optimizing combination immunotherapies to enhance cancer therapeutic effectiveness, particularly in solid tumor therapies where MDSCs are highly prevalent. 

摘要翻译：

尽管癌症免疫疗法在治疗血液恶性肿瘤方面取得了成功，但由于免疫抑制性肿瘤微环境（主要由髓源性抑制细胞（MDSCs）形成）的存在，其在实体瘤中的疗效仍然有限。MDSCs不仅通过强大的免疫抑制作用阻碍了免疫检查点抑制剂（ICIs）和适应性细胞疗法的成功，还通过非免疫途径促进肿瘤进展，包括促进血管生成、驱动上皮-间质转化（EMT）以及参与建立转移前微环境。虽然单独靶向MDSCs或与传统疗法联合应用取得的成效有限，但新出现的证据表明，MDSCs检查点阻断与其他免疫疗法联合应用，在克服免疫和非免疫障碍方面具有巨大潜力。本综述讨论了MDSCs的双重作用，特别关注了尚未充分探索的检查点阻断策略。我们探讨了联合策略的理论基础、其在克服MDSC介导的免疫抑制方面的潜在优势以及相关开发挑战。此外，我们重点提出了未来研究方向，旨在优化联合免疫疗法以提高癌症治疗效果，尤其是在MDSCs高度 prevalent的实体瘤治疗领域。

原文链接：

MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy