Inhibition of tumor-induced myeloid-derived suppressor cell function by a nanoparticulated adjuvant.
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.
Center of Molecular Immunology, Havana 11600, Cuba. audry@cim.sld.cu
Audry
A
Fernández
Circe
C
Mesa
Ilaria
I
Marigo
Luigi
L
Dolcetti
Marilyn
M
Clavell
Liliana
L
Oliver
Luis E
LE
Fernández
Vincenzo
V
Bronte
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D005679:G(M3) Ganglioside / Q000008:administration & dosage / Q000276:immunology; D006131:Growth Inhibitors / Q000008:administration & dosage; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage*; D009345:Neisseria meningitidis / Q000276:immunology; D011510:Proteolipids / Q000008:administration & dosage* / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D006131:Growth Inhibitors; D011510:Proteolipids; C020485:proteoliposomes