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

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590994
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: KYOTO UNIVERSITY
• Principal Investigator: KADOWAKI Norimitsu Kyoto University, Department of Medicine, Lecturer, 医学研究科, 講師 (60324620)
• Project Period (FY): 2005 – 2006
• Keywords: tumor immunology / immune tolerance / T cells / interferon-α / β / myeloid cells

Research Abstract

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.