Peripheral blood mononuclear cells of patients with breast cancer can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells
| Autor: | Wen Wan, Christine K. Zoon, Khin Marlar, Mehrab Nasiri Kenari, Harry D. Bear, A. Latif Kazim, Masoud H. Manjili, Kyle K. Payne, Rebecca C. Keim |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Receptor ErbB-2 medicine.medical_treatment Breast Neoplasms chemical and pharmacologic phenomena Biology Lymphocyte Activation Immunotherapy Adoptive Article Interleukin 21 Cancer immunotherapy medicine Humans Myeloid Cells IL-2 receptor Neoplasm Staging Interleukin-15 Interleukin-7 Ionomycin hemic and immune systems Dendritic Cells Immunotherapy Bryostatins Natural killer T cell NKG2D Lymphocyte Subsets Tumor Burden Oncology Immunology Leukocytes Mononuclear Myeloid-derived Suppressor Cell Interleukin 12 Interleukin-2 Natural Killer T-Cells Female |
| Zdroj: | Breast Cancer Research and Treatment. 142:45-57 |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | Two major barriers in the immunotherapy of breast cancer include tumor-induced immune suppression and the establishment of long-lasting immune responses against the tumor. Recently, we demonstrated in an animal model of breast carcinoma that expanding and reprogramming tumor-sensitized lymphocytes, ex vivo, yielded T memory (Tm) cells as well as activated CD25+ NKT cells and NK cells. The presence of activated CD25+ NKT and NK cells rendered reprogrammed T cells resistant to MDSC-mediated suppression, and adoptive cellular therapy (ACT) of reprogrammed lymphocytes protected the host from tumor development and relapse. Here, we performed a pilot study to determine the clinical applicability of our protocol using peripheral blood mononuclear cells (PBMCs) of breast cancer patients, ex vivo. We show that bryostatin 1 and ionomycin (B/I) combined with IL-2, IL-7 and IL-15 can expand and reprogram tumor-sensitized PBMCs. Reprogrammed lymphocytes contained activated CD25+ NKT and NK cells as well as Tm cells and displayed enhanced reactivity against HER-2/neu in the presence of MDSCs. The presence of activated NKT cells was highly correlated with the rescue of anti-HER-2/neu immune responses from MDSC suppression. Ex vivo blockade experiments suggest that the NKG2D pathway may play an important role in overcoming MDSC suppression. Our results show the feasibility of reprogramming tumor-sensitized immune cells, ex vivo, and provide rationale for ACT of breast cancer patients. |
| Databáze: | OpenAIRE |
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