Inhibition of Tumor-Induced Myeloid-Derived Suppressor Cell Function by a Nanoparticulated Adjuvant

Abstract

The interaction between cancer vaccine adjuvants and myeloid-derived suppressor cells (MDSCs) is currently poorly understood. Very small size proteoliposomes (VSSP) are a nanoparticulated adjuvant under investigation in clinical trials in patients with renal carcinoma, breast cancer, prostate cancer, and cervical intraepithelial neoplasia grade III. We found that VSSP adjuvant induced a significant splenomegaly due to accumulation of CD11b+Gr-1+ cells. However, VSSP-derived MDSCs showed a reduced capacity to suppress both allogeneic and Ag-specific CTL response compared with that of tumor-induced MDSCs. Moreover, splenic MDSCs isolated from tumor-bearing mice treated with VSSP were phenotypically more similar to those isolated from VSSP-treated tumor-free mice and much less suppressive than tumor-induced MDSCs, both in vitro and in vivo. Furthermore, different from dendritic cell vaccination, inoculation of VSSP-based vaccine in EG.7-OVA tumor-bearing mice was sufficient to avoid tumor-induced tolerance and stimulate an immune response against OVA Ag, similar to that observed in tumor-free mice. This effect correlated with an accelerated differentiation of MDSCs into mature APCs that was promoted by VSSP. VSSP used as a cancer vaccine adjuvant might thus improve antitumor efficacy not only by stimulating a potent immune response against tumor Ags but also by reducing tumor-induced immunosuppression.

Circulating Myeloid-Derived Suppressor Cells Are Increased and Activated in Pulmonary Hypertension

“…20 PH is associated with infl ammation 21 and autoimmunity, 22 and can be induced by antigenic challenge via airway ovalbumin. 23 We hypothesized that individuals with PH would have increased circulating MDSCs.…”

Cyclooxygenase Inhibition in Cancer Immunotherapy: Combination of Indomethacin with Cancer Vaccines Is Not Always Beneficial

“…This adjuvant has been proved to promote dendritic cell (DC) maturation, antigen cross presentation to CD8+ T cells, T helper (Th) polarization, enhance cytotoxic T lymphocyte (CTL) response [32] [33] and induce a repopulation of immune cells in leukopenic scenarios [34] while simultaneously abrogating the immunosuppressive capacity of myeloid-derived suppressor cells [35].…”

Nanotechnology Approaches for Cancer Immunotherapy and Immunomodulation

“…VSSP were proved to modulate the suppressive activity of tumor-derived MDSCs in mice by inducing their differentiation to APCs (Fernández et al 2011(Fernández et al , 2013, and on the basis of these results, the development of a vaccine able to target these immunosuppressive cells whilst eliciting an immune response towards the associated antigen has been proposed.…”