Antigen-specific immunity and cross-priming by epithelial ovarian carcinoma-induced CD11b(+)Gr-1(+) cells.
Both innate and adaptive immune systems are considered important for cancer prevention, immunosurveillance, and control of cancer progression. It is known that, although both systems initially eliminate emerging tumor cells efficiently, tumors eventually escape immune attack by a variety of mechanisms, including differentiation and recruitment of immunosuppressive CD11b(+)Gr-1(+) myeloid suppressor cells into the tumor microenvironment. However, we show that CD11b(+)Gr-1(+) cells found in ascites of epithelial ovarian cancer-bearing mice at advanced stages of disease are immunostimulatory rather than being immunosuppressive. These cells consist of a homogenous population of cells that morphologically resemble neutrophils. Moreover, like dendritic cells, immunostimulatory CD11b(+)Gr-1(+) cells can strongly cross-prime, augmenting the proliferation of functional CTLs via signaling through the expression of costimulatory molecule CD80. Adoptive transfer of these immunostimulatory CD11b(+)Gr-1(+) cells from ascites of ovarian cancer-bearing mice results in the significant regression of s.c. tumors even without being pulsed with exogenous tumor Ag prior to adoptive transfer. We now show for the first time that adaptive immune responses against cancer can be augmented by these cancer-induced granulocyte-like immunostimulatory myeloid (CD11b(+)Gr-1(+)) cells, thereby mediating highly effective antitumor immunity in an adoptive transfer model of immunity.
Tomihara
Kei
K
Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Guo
Miao
M
Shin
Takako
T
Sun
Xiuhua
X
Ludwig
Sara M
SM
Brumlik
Michael J
MJ
Zhang
Bin
B
Curiel
Tyler J
TJ
Shin
Tahiro
T
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology*; D002469:Cell Separation; D045142:Cross-Priming / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine