Endothelial cell senescence is characterized by acquisition of 
senescence-associated secretory phenotype (SASP), able to promote inflammaging 
and cancer progression. Emerging evidence suggest that preventing SASP 
development could help to slow the rate of aging and the progression of 
age-related diseases, including cancer. Aim of this study was to evaluate 
whether and how adalimumab, a monoclonal antibody directed against tumor 
necrosis factor-α (TNF-α), a major SASP component, can prevent the SASP. A 
three-pronged approach has been adopted to assess the if adalimumab is able to: 
i) modulate a panel of classic and novel senescence- and SASP-associated markers 
(interleukin [IL]-6, senescence associated-β-galactosidase, p16/Ink4a, 
plasminogen activator inhibitor 1, endothelial nitric oxide synthase, 
miR-146a-5p/Irak1 and miR-126-3p/Spred1) in human umbilical vein endothelial 
cells (HUVECs); ii) reduce the paracrine effects of senescent HUVECs' secretome 
on MCF-7 breast cancer cells, through wound healing and mammosphere assay; and 
iii) exert significant decrease of miR-146a-5p and increase of miR-126-3p in 
circulating angiogenic cells (CACs) from psoriasis patients receiving adalimumab 
in monotherapy.TNF-α blockade associated with adalimumab induced significant 
reduction in released IL-6 and significant increase in eNOS and miR-126-3p 
expression levels in long-term HUVEC cultures.A significant reduction in 
miR-146a-5p expression levels both in long-term HUVEC cultures and in CACs 
isolated from psoriasis patients was also evident. Interestingly, conditioned 
medium from senescent HUVECs treated with adalimumab was less consistent than 
medium from untreated cells in inducing migration- and mammosphere- promoting 
effects on MCF-7 cells.Our findings suggest that adalimumab can induce 
epigenetic modifications in cells undergoing senescence, thus contributing to 
the attenuation of SASP tumor-promoting effects.