Activated NKT cells and NK cells render T cells resistant to myeloid-derived suppressor cells and result in an effective adoptive cellular therapy against breast cancer in the FVBN202 transgenic mouse.
Publication/Presentation Date
7-15-2011
Abstract
Attempts to cure breast cancer by adoptive cellular therapy (ACT) have not been successful. This is primarily due to the presence of tumor-induced immune-suppressive mechanisms as well as the failure of tumor-reactive T cells to provide long-term memory responses in vivo. To address these clinically important challenges, we developed an ex vivo protocol for the expansion of tumor-reactive immune cells obtained from tumor-bearing animals prior to or after local radiation therapy. We used an Ag-free protocol that included bryostatin 1/ionomycin and sequential common γ-chain cytokines (IL-7/IL-15 + IL-2). The proposed protocol expanded tumor-reactive T cells as well as activated non-T cells, including NKT cells, NK cells, and IFN-γ-producing killer dendritic cells. Antitumor efficacy of T cells depended on the presence of non-T cells. The effector non-T cells also rendered T cells resistant to myeloid-derived suppressor cells. Radiation therapy altered phenotypic distribution and differentiation of T cells as well as their ability to generate central memory T cells. ACT by means of the expanded cells protected animals from tumor challenge and generated long-term memory responses against the tumor, provided that leukocytes were derived from tumor-bearing animals prior to radiation therapy. The ex vivo protocol was also able to expand HER-2/neu-specific T cells derived from the PBMC of a single patient with breast carcinoma. These data suggest that the proposed ACT protocol should be studied further in breast cancer patients.
Volume
187
Issue
2
First Page
708
Last Page
717
ISSN
1550-6606
Published In/Presented At
Kmieciak, M., Basu, D., Payne, K. K., Toor, A., Yacoub, A., Wang, X. Y., Smith, L., Bear, H. D., & Manjili, M. H. (2011). Activated NKT cells and NK cells render T cells resistant to myeloid-derived suppressor cells and result in an effective adoptive cellular therapy against breast cancer in the FVBN202 transgenic mouse. Journal of immunology (Baltimore, Md. : 1950), 187(2), 708–717. https://doi.org/10.4049/jimmunol.1100502
Disciplines
Medicine and Health Sciences
PubMedID
21670315
Department(s)
Department of Medicine, Hematology-Medical Oncology Division
Document Type
Article