Antigen-Specific Immunity and Cross-Priming by Epithelial Ovarian Carcinoma-Induced CD11b+Gr-1+ Cells

Abstract

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.

Potential therapeutic anti-tumor effect of aSalmonella-based vaccine

“…In this regard, Salmonella-based anti-tumor immunotherapies shed light on the development of effective ways to treat tumor patients, in that they can specifically target and colonize the tumor site, promote an inflammatory response by inducing infiltration of neutrophils, induce tumor-specific T-cell responses and 20 In a cancer model, immunogenic MDSCs mediating antitumor immunity were generated in epithelial ovarian cancer-bearing mice. 43 In our recently reported study, 15 we detected an accumulation of distinct TNF-α-producing Ly6-G high Ly6-C inter MDSCs in mice treated with intratumoral RASV (Fig. 2), and they exhibited a therapeutic antitumor effect.…”

Leukocytes Infiltrate the Skin and Draining Lymph Nodes in Response to the ProtozoanLeishmania infantum chagasi

“…affect neutrophil functions such as release of chemokines and consequent recruitment of macrophages and immature dendritic cells to the infection site (11,35). Neutrophil-like polymorphonuclear CD11b ϩ Gr1 ϩ leukocytes can also function in antigen presentation and cross-priming, with consequent cytotoxic T lymphocyte (CTL) activation (44).…”

Immune Therapy for Ovarian Cancer: Promise and Pitfalls

“…There is interest in depleting myeloid-derived suppressor cells as anti-tumor therapy [112]. However, ID8-induced myeloid derived suppressor cells were inhibitory as expected in one lab [114], whereas we found them to be immune stimulatory [113]. Further work is required to understand mechanisms for their generation in tumors and to understand differences in different in vivo systems to help advance this strategy towards human OC applications.…”

“…[112]. These cells are generated in humans with OC and in mouse OC models [113,114]. There is interest in depleting myeloid-derived suppressor cells as anti-tumor therapy [112].…”