Depletion of dendritic cells delays ovarian cancer progression by boosting antitumor immunity.
Dendritic cells (DC) and cytokines that expand myeloid progenitors are widely used to treat cancer. Here, we show that CD11c(+)DEC205(+) DCs coexpressing alpha-smooth muscle actin and VE-cadherin home to perivascular areas in the ovarian cancer microenvironment and are required for the maintenance of tumor vasculature. Consequently, depletion of DCs in mice bearing established ovarian cancer by targeting different specific markers significantly delays tumor growth and enhances the effect of standard chemotherapies. Tumor growth restriction was associated with vascular apoptosis after DC ablation followed by necrosis, which triggered an antitumor immunogenic boost. Our findings provide a mechanistic rationale for selectively eliminating tumor-associated leukocytes to promote antitumor immunity while impeding tumor vascularization and to develop more effective DC vaccines based on a better understanding of the tumor microenvironment.
Huarte
Eduardo
E
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 03766, USA.
Cubillos-Ruiz
Juan R
JR
Nesbeth
Yolanda C
YC
Scarlett
Uciane K
UK
Martinez
Diana G
DG
Buckanovich
Ronald J
RJ
Benencia
Fabian
F
Stan
Radu V
RV
Keler
Tibor
T
Sarobe
Pablo
P
Sentman
Charles L
CL
Conejo-Garcia
Jose R
JR