Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 58, Issue 6, Pages 941-953Publisher
SPRINGER
DOI: 10.1007/s00262-008-0609-z
Keywords
Adoptive immunotherapy; Breast cancer; Myeloid-derived suppressor cells; HER-2/neu; Gamma chain cytokines
Categories
Funding
- NIH [R01 CA104757, P30CA16059]
- VCU Massey Cancer Centre
- Commonwealth Foundation for Cancer Research
- Department of Defense [BC083048]
Ask authors/readers for more resources
Adoptive immunotherapy (AIT) using ex vivo-expanded HER-2/neu-specific T cells has shown initial promising results against disseminated tumor cells in the bone marrow. However, it has failed to promote objective responses against primary tumors. We report for the first time that alternating gamma chain cytokines (IL-2, IL-7 and IL-15) ex vivo can expand the neu-specific lymphocytes that can kill breast tumors in vitro. However, the anti-tumor efficacy of these neu-specific T cells was compromised by the increased levels of myeloid-derived suppressor cells (MDSC) during the premalignant stage in FVBN202 transgenic mouse model of breast carcinoma. Combination of AIT with the depletion of MDSC, in vivo, resulted in the regression of neu positive primary tumors. Importantly, neu-specific antibody responses were restored only when AIT was combined with the depletion of MDSC. In vitro studies determined that MDSC caused inhibition of T cell proliferation in a contact-dependent manner. Together, these results suggest that combination of AIT with depletion or inhibition of MDSC could lead to the regression of mammary tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available