O desenvolvimento do câncer está associado a falhas no sistema imune. Investigamos como o microambiente tumoral de mama afetaria a diferenciação de monócitos. Observamos que a alta frequência de macrófagos (MΦ) CD163⁺ associou-se à baixa sobrevida das pacientes e a um baixo infiltrado de células T CD3⁺ nos tumores. Sobrenadantes obtidos da dilaceração des tumores (SNDil) induziram a diferenciação de monócitos para MΦ CD163^highIL-10^high, os quais suprimiram células T CD4⁺. O fenótipo CD163^highIL-10^high associou-se a altos níveis de M-CSF, TGF-β e VEGF nos tumores. Monócitos circulantes de pacientes falharam em diferenciar-se em M1-M Φ; deram origem à DCs capazes de induzir alta frequência de células T reguladoras (Tregs) e produziram altos níveis de citocinas anti-inflamatórias sob ativação por LPS. Em conclusão, o microambiente tumoral favorece a diferenciação de MΦ CD163^highIL-10^high supressivos e afeta sistemicamente o potencial de diferenciação de monócitos de pacientes.

Cancer development is associated with failures in the immune system. We investigated here if breast tumor microenvironment affect the differentiation of monocytes. We observed that the high frequency of macrophages (MΦ) CD163⁺ was associated with poor patients survival and a low infiltration of CD3⁺ T cells in tumors. Supernatants obtained from dilacerated tumors (SNDil) skewed the differentiation of monocytes into CD163^highIL10^high MΦ, which suppressed CD4⁺ T cells. The CD163^highIL-10^high phenotype was associated with high levels of M-CSF, TGF-β and VEGF in tumors. Circulating monocytes from patients failed to differentiate into M1-MΦ; gave rise to DCs able to induce high frequency of regulatory T cells (Tregs) and produced high levels of anti-inflammatory cytokines under LPS activation. In conclusion, the tumor microenvironment promotes the differentiation of suppressive CD163^highIL10^high MΦ and affects the potential of differentiation of patients' monocytes systemically.