Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, Vago L, Nebuloni M, Mantovani A, Sica AA distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107: 2112-2122

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Blood (Impact Factor: 10.45). 04/2006; 107(5):2112-22. DOI: 10.1182/blood-2005-01-0428
Source: PubMed


To identify the molecular basis underlying the functions of tumor-associated macrophages (TAMs), we characterized the gene expression profile of TAMs isolated from a murine fibrosarcoma in comparison with peritoneal macrophages (PECs) and myeloid suppressor cells (MSCs), using a cDNA microarray technology. Among the differentially expressed genes, 15 genes relevant to inflammation and immunity were validated by real-time polymerase chain reaction (PCR) and protein production. Resting TAMs showed a characteristic gene expression pattern with higher expression of genes coding for the immunosuppressive cytokine IL-10, phagocytosis-related receptors/molecules (Msr2 and C1q), and inflammatory chemokines (CCL2 and CCL5) as expected, as well as, unexpectedly, IFN-inducible chemokines (CXCL9, CXCL10, CXCL16). Immunohistology confirmed and extended the in vitro analysis by showing that TAMs express M2-associated molecules (eg, IL-10 and MGL1), as well as CCL2, CCL5, CXCL9, CXCL10, and CXCL16, but no appreciable NOS2. Lipopolysaccharide (LPS)-mediated activation of TAMs resulted in defective expression of several proinflammatory cytokines (eg, IL-1beta, IL-6, TNF-alpha) and chemokines (eg, CCL3), as opposed to a strong up-regulation of immunosuppressive cytokines (IL-10, TGFbeta) and IFN-inducible chemokines (CCL5, CXCL9, CXCL10, CXCL16). Thus, profiling of TAMs from a murine sarcoma revealed unexpected expression of IFN-inducible chemokines, associated with an M2 phenotype (IL-10high, IL-12low), and divergent regulation of the NF-kappaB versus the IRF-3/STAT1 pathway.

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Available from: Tiziana Schioppa, Jan 21, 2014
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    • "Isolation of monocytes and culture of hMDMs and BMDMs p27 kip1+ / + , p27 kip12 / 2 , p27 kip1 Ser10Ala and p27 kip1 CK 2 mice have been previously described ( Biswas et al . , 2006 ; Fero et al . , 1996 ) . Human monocytes were isolated from blood of healthy donors ( buffy coat obtained from Etablissement Français du Sang , Toulouse , France ) and differentiated into human monocyte - derived macrophages ( hMDMs ) as previously described ( Van Goethem et al . , 2010 ) . Blood samples were obtained following standar"
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    • "Similarly, some M1 markers were upregulated in ovarian TAMs, such as CD86 and TNF. This mixed-polarization phenotype has also been described in other tumor types (29–32), and suggests that TAMs most closely resemble macrophages involved in developmental processes. "
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    • "There is an ever-increasing understanding of these endogenous molecular pathways initiated by polarising factors such as IL-4. Whereas p65 NFκB subunit expression is associated with M1 polarisation, M2 polarisation has been described to be orchestrated by p50 NFκB [30] [31], whereby p50 NFκB inhibits NFκB-dependent M1 polarisation. In addition, p50- deficient mice exhibit exacerbated M1-driven inflammatory responses with a concomitant suppression of M2-driven responses (allergy and anti-helminth immunity). "

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