Role of Myeloid-Derived Suppressor Cells in the Immunotherapy of HER2/neu-Positive Breast Carcinomas

摘要

We have found myeloid-derived suppressor cells (MDSC) to be the major inhibitors of adoptively transferred anti-HER2/neu T cells in vivo. Depletion of these cells results in tumor inhibition coupled with increased anti-HER2/neu antibody titers. Significantly, we have found that the combination of the chemotherapeutic drug gemcitabine, which selectively inhibits MDSC, with adoptive immunotherapy results in complete tumor rejection, elevated antibody titers, and immunological memory capable of rejecting further tumor challenge. Additionally, the generation of de novo MDSC from the bone marrow is dependent on GM-CSF, which is frequently used as an adjuvant in the immunotherapy setting. Based on these findings, we propose that the use of GM- CSF with immunotherapies be re-evaluated and suggest that immunotherapy should be administered in conjunction with gemcitabine for the inhibition of MDSC.