Myeloid-derived suppressor cells in cancer cachexia syndrome: a new explanation for an old problem.
Cachexia accompanies many chronic inflammatory diseases, including cancer. Lean tissue wasting is only one component of the cancer cachexia response, which also includes anemia, anorexia, a hepatic acute phase protein response, and increased susceptibility to secondary infections. The etiologies of cancer cachexia are multifactorial and include an overproduction of inflammatory mediators, including cytokines produced by inappropriate activation of innate immunity. However, anticytokine therapies have generally not been seriously considered for cancer cachexia, in large part because of the overlapping activities of several inflammatory cytokines and the inability to prospectively identify the contributions of individual mediators. In contrast, recent evidence has focused on an immature myeloid cell population that expands dramatically in the tumors and secondary lymphoid organs of animals with some actively growing tumors. These immature GR-1(+)CD11b(+) cells are metabolically active and secrete large quantities of inflammatory cytokines and chemokines with the potential to produce cachexia. Their expansion is temporally associated with the development of cachexia. Future studies are required to determine whether therapeutic efforts intended to block the expansion of these cells can prevent the lean tissue wasting that accompanies active tumor growth.
Winfield
Robert D
RD
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610-0286, USA.
Delano
Matthew J
MJ
Pande
Kalyan
K
Scumpia
Philip O
PO
Laface
Drake
D
Moldawer
Lyle L
LL
D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000378:metabolism; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology
D000209:Acute-Phase Proteins; D016207:Cytokines; D018836:Inflammation Mediators