Analysis of myeloid suppressor cells in tumor-bearing mice and humans and in patients after chemotherapy

荷瘤小鼠和人类以及化疗后患者的骨髓抑制细胞分析

• 批准号: 17590994
• 负责人: KADOWAKI Norimitsu
• 金额: $ 1.92万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590994/
• 关键词: tumor immunology; immune tolerance; T cells; interferon-α; β; myeloid cells; 腫瘍免役; 免役寛容; インターフェロンα

Immunosuppressive cell types, which physiologically down-regulate excessive immune responses, hamper the development of effective anti-tumor immunity. CD11b^+Gr-1^+ immature myeloid suppressor cells (MSCs) increase in mice bearing various types of cancers, and have been shown to suppress anti-tumor T cell responses by several mechanisms. Thus, measures that inhibit the function of MSCs are important to enhance anti-tumor immune responses.Initially, we observed that type I interferon (IFN-α/β) reversed the suppressive effect of MSCs from CT26 (colon cancer cell line)-bearing BALB/c mice on T cell proliferation. Since exposure of MSCs but not T cells to IFN-β was sufficient to reverse the suppressive effect of MSCs, IFN-β was likely to directly act on MSCs.During experiments, however, we became unable to observe the increase in MSCs in tumor-bearing mice. Furthermore, after overcoming this problem, we became unable to observe the reversal of the immunosuppressive effect of MSCs by type I IFN. Therefore, we conclude that our initial observation that type I IFN diminishes the immunosuppressive effect of MSCs is not a physiologically meaningful, reproducible phenomenon. The reason why we initially observed the suppressive effect of type I IFN on MSCs is unknown.

在生理上下调过度免疫应答的免疫抑制细胞类型阻碍有效抗肿瘤免疫的发展。CD 11b ^+Gr-1^+未成熟骨髓抑制细胞（MSC）在携带各种类型癌症的小鼠中增加，并且已被证明通过多种机制抑制抗肿瘤T细胞反应。因此，抑制骨髓间充质干细胞的功能对于增强抗肿瘤免疫应答是非常重要的。最初，我们观察到I型干扰素（IFN-α/β）逆转了来自携带CT 26（结肠癌细胞系）的BALB/c小鼠的骨髓间充质干细胞对T细胞增殖的抑制作用。由于MSC暴露于IFN-β而不是T细胞暴露于IFN-β足以逆转MSC的抑制作用，因此IFN-β可能直接作用于MSC。然而，在实验期间，我们无法观察到荷瘤小鼠中MSC的增加。此外，在克服这个问题后，我们无法观察到I型IFN对MSC的免疫抑制作用的逆转。因此，我们的结论是，我们最初的观察，即I型干扰素减少骨髓间充质干细胞的免疫抑制作用是不是一个生理上有意义的，可重复的现象。我们最初观察到I型IFN对MSC的抑制作用的原因尚不清楚。