Cholinergic Actions of Autoantibodies from Breast Cancer Patients on Dendritic Cells

Abstract

Autoantibodies (autoAbs) against self-proteins have been localized in tumor microenvironment exerting a complex network of interactions. We reported the presence of autoAbs in breast cancer patients, which promote tumor progression by activating muscarinic acetylcholine receptors (mAChR) in tumor cells. Cholinergic receptors are also expressed in dendritic cells (DC) and much clear evidence demonstrated a deficient functional activity of DC in cancer. Here we investigated whether autoAbs can modulate the expression of maturation markers and the production of cytokines by DC. IgG from breast cancer patients in stage I reduced the expression of HLA-DR and CD86 as well as tumor necrosis factor alpha liberation and augmented interleukin IL-12 and IL-10 levels by cholinergic activation of mature DC. The latter cytokines are also up-regulated in patients' sera, probably due to tumor influence, since the addition of breast tumor extract increased cytokine levels in immature DC reaching levels of mature DC mainly for IL-10 and IL-12. It could be assumed that autoAbs are reinforcing the tolerogenic/ immunosuppressive profile mediated by DC in breast cancer.