病理激活的中性粒细胞上表达的CD300ld参与肿瘤免疫抑制

The CD300ld Receptor on Pathologically Activated Neutrophils is Required for Tumor-Driven Immune Suppression

通过靶向免疫检查点分子进而增强免疫效应细胞的肿瘤细胞杀伤能力是近年来肿瘤治疗领域的重大突破。然而,肿瘤内部高度免疫抑制性的肿瘤微环境使得现有的免疫检查点阻断疗法效果不佳。肿瘤的微环境高度异质,而大量浸润的髓系细胞在免疫抑制微环境的建立上发挥关键作用,其中病理激活的中性粒细胞[也被称为多形核髓系来源的抑制细胞(polymor-phonuclear myeloid-derived suppressor cell,PMN-MDSC)]是微环境的重要组分。不同于正常的中性粒细胞,PMN-MDSC具有强烈的抑制淋巴细胞杀伤功能的作用。因此,寻找特异且高效地阻断PMN-MDSC的靶点是当前免疫治疗研究中的热点。该文总结了该团队发现PMN-MDSC上表达的膜蛋白CD300ld参与肿瘤发展的过程,并详细描述了CD300ld通过下游S100A8/A9发挥功能的信号转导机制。靶向CD300ld有可能成为一种有潜力的肿瘤治疗手段,为后续的免疫治疗提供了新思路。

Targeting immune checkpoint proteins to enhance the cytotoxic ability of immune effector cells represents a breakthrough in cancer therapy and has achieved promising results in clinical treatments.However,a significant proportion of cancer patients do not respond to existing immune checkpoint inhibitor therapy due to the highly immunosuppressive tumor microenvironment.This microenvironment is heterogeneous,and myeloid cells play a key role in its establishment,particularly pathologically activated neutrophil,also known as PMN-MDSC(polymorphonuclear myeloid-derived suppressive cell),which is recognized as the major immune suppressor.Unlike normal neutrophils,PMN-MDSC has a strong suppressive ability to lymphocytes.Therefore,identifying specific and effective targets to block PMN-MDSC in the tumor microenvironment is an important avenue of immunotherapy research.This article summarizes the team’s discovery of the membrane protein CD300ld expressed on PMN-MDSC involved in tumor development,and describes in detail the signal transduction mechanism by which CD300ld functions through downstream S100A8/A9.Targeting CD300ld may potentially become a promising tumor treatment approach,providing new insights for subsequent immunotherapy.