Using myeloma mouse model, Haabeth and Henning et al. show, with adoptive transfer or TCR-transgenic (TCR-Tg) mice, that tumor-specific CD4+ T cells elicit antitumor immune response in the bone marrow (BM) via activation of BM-resident macrophages but not neutrophils, eosinophils, or NK cells. Antitumor immunity of CD4+ T cells was dependent on IFNγ and asialo GM1 (AGM1)-expressing CD11b+ macrophages. AGM1+CD11b+ cells from tumor-challenged TCR-Tg mice showed increased MHC-II expression and tumor-specific antigen presentation. Depletion of (Ly6G/C) Gr-1+ monocyte-derived cells led to loss of antitumor immune response in the BM.
Contributed by Shishir Pant
ABSTRACT: CD4+ T cells may induce potent antitumor immune responses through interaction with antigen-presenting cells within the tumor microenvironment. Using a murine model of multiple myeloma, we demonstrated that adoptive transfer of idiotype-specific CD4+ T cells may elicit curative responses against established multifocal myeloma in bone marrow. This finding indicates that the myeloma bone marrow niche contains antigen-presenting cells that may be rendered tumoricidal. Given the complexity of the bone marrow microenvironment, the mechanistic basis of such immunotherapeutic responses is not known. Through a functional characterization of antitumor CD4+ T-cell responses within the bone marrow microenvironment, we found that killing of myeloma cells is orchestrated by a population of bone marrow-resident CD11b+F4/80+MHC-IIHigh macrophages that have taken up and present secreted myeloma protein. The present results demonstrate the potential of resident macrophages as powerful mediators of tumor killing within the bone marrow and provide a basis for novel therapeutic strategies against multiple myeloma and other malignancies that affect the bone marrow.
Author Info: (1) Department of Immunology and Transfusion Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Division of Oncology, Department of Medicine, Stanford Cancer Institu
Author Info: (1) Department of Immunology and Transfusion Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA. (2) Department of Immunology and Transfusion Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. (3) Department of Immunology and Transfusion Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. K. G. Jebsen Centre for B cell Malignancies, Oslo University Hospital, Rikshospitalet, Oslo, Norway; and. (4) Department of Biosciences and. (5) Department of Immunology and Transfusion Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo, Norway. (6) Department of Immunology and Transfusion Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. K. G. Jebsen Centre for B cell Malignancies, Oslo University Hospital, Rikshospitalet, Oslo, Norway; and.
