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

免疫抑制细胞类型，其生理上下调过度的免疫反应，阻碍了有效的抗肿瘤免疫的发展。CD11b^+Gr-1^+未成熟髓样抑制细胞（MSCs）在各种类型癌症小鼠中增加，并且已被证明通过几种机制抑制抗肿瘤T细胞反应。因此，抑制MSCs功能的措施对于增强抗肿瘤免疫反应是重要的。最初，我们观察到I型干扰素（IFN-α/β）逆转了来自CT26（结肠癌细胞系）的BALB/c小鼠的MSCs对T细胞增殖的抑制作用。由于MSCs而非T细胞暴露于IFN-β足以逆转MSCs的抑制作用，因此IFN-β可能直接作用于MSCs。然而，在实验中，我们无法观察到荷瘤小鼠中MSCs的增加。此外，在克服了这个问题之后，我们无法观察到I型IFN对MSCs免疫抑制作用的逆转。因此，我们得出结论，我们最初观察到的I型IFN减少MSCs的免疫抑制作用并不是一个有生理学意义的、可重复的现象。我们最初观察到I型IFN对MSCs抑制作用的原因尚不清楚。

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.