The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance.
An intrinsic (oncogene-driven) pathway and an extrinsic (microenvironment-driven) pathway connect inflammatory reactions and cancer. M2-polarized tumor-associated macrophages and the related myeloid-derived suppressor cells are key prototypic components of smoldering inflammation driving neoplastic progression. However, mononuclear phagocytes can exert anti-tumor activity by killing tumor cells and eliciting tissue disruptive reactions (M1), a likely scenario in the early phases of carcinogenesis of immunogenic tumors and following therapeutic intervention. Shifting the macrophage balance represents a viable therapeutic target. Herein, the 'macrophage balance' is discussed in the context of the apparent paradox of tumor promotion by innate immunity-driven inflammation and the seemingly opposed tumor surveillance by adaptive immune responses.
Allavena
Paola
P
Istituto Clinico Humanitas IRCCS, Rozzano, Milan, Italy.
Sica
Antonio
A
Garlanda
Cecilia
C
Mantovani
Alberto
A
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D005260:Female; D012739:Gonadal Steroid Hormones / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007157:Immunologic Surveillance; D007249:Inflammation; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000276:immunology; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D019139:Tumor Escape; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
D016207:Cytokines; D012739:Gonadal Steroid Hormones; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases