New Roles for Mononuclear Phagocytes in Cancer Biology

Abstract

The primary focus in the pathogenesis and treatment of human malignancies has been the tumor cell. However, the biologic properties of a malignancy are not all intrinsically determined. Interactions between heterogeneous cell populations influence the growth and survival of both normal and malignant cells. Studies defining the origin of endothelial cells involved in tumor angiogenesis first demonstrated the contributions of normal cellular environment. Recently, the mononuclear phagocyte lineage has been found to have biologically and clinically significant tumor enhancing and tumor suppressive effects. This article reviews the multiple roles of mononuclear phagocytes in cancer biology. A companion manuscript (J Pediatr Hematol Oncol. 2008, in press) describes the targeting of these cells for therapeutic benefit. Incorporating these strategies into future childhood cancer protocols could be an innovative approach for improving patient outcome.

Doxorubicin treatment induces tumor cell death followed by immunomodulation in a murine neuroblastoma model

“…These innate cellular phagocytes are considered to have a pivotal role in the mechanism of tumor immunity (2,14–17). In particular, BM-derived immature DCs phagocytose, mature and later contribute to immune reactions against cancer cells (2,13,18,19).…”

“…These innate cellular phagocytes are considered to have a pivotal role in the mechanism of tumor immunity (2,14–17). In particular, BM-derived immature DCs phagocytose, mature and later contribute to immune reactions against cancer cells (2,13,18,19). Alternatively, tumor-associated macrophages infiltrate the tumor, engulfing dead cells and inducing a tolerogenic reaction to tumor cells (15,16,20).…”

“…In particular, apoptosis and necrosis have significantly different effects on the subsequent immunological response (1,2). Apoptotic cells are commonly engulfed by phagocytes, such as macrophages or dendritic cells (DCs), which induce a sequential immune response (1,2). Whether the engulfed apoptotic cells induce subsequent tolerogenicity or immunogenicity depends on the function of the phagocytes involved.…”

“…Whether the engulfed apoptotic cells induce subsequent tolerogenicity or immunogenicity depends on the function of the phagocytes involved. Furthermore, it has been revealed that the mechanisms of cell death induced by chemotherapeutic antitumor agents have an effect on the immunogenicity of dying tumor cells (2–4). Obeid et al (5) and Martins et al (6) reported that anthracyclins induce immunogenic tumor cell death in a murine colon cancer model.…”

Markers of Monocyte Activation Revealed by Lipidomic Profiling of Arachidonic Acid-Containing Phospholipids

“…T he key role that monocytes play in inflammation and related diseases is well established (1,2), and these cells can also constitute a target for therapeutic strategies in cancer (3). The role of monocytes as immunomodulatory cells has been related, at least in part, to their capacity to synthesize and release large amounts of arachidonic acid (AA)-derived eicosanoid mediators (4).…”