IntroductionTumour associated macrophages (TAMs) are an important part of the tumour microenvironment in most cancers. It has been shown that TAMs are mostly anti-inflammatory M2-like macrophages. It is clearly known that M2 macrophages in tumour can inhibit immune responses but the direct effect of these M2 macrophages on cancer cell response to chemotherapeutic drugs is still unknown.Material and methodsThe aim on this work is to characterise for the first time the direct effect of TAMs on cancer cell chemoresistance. Here, we used THP-1 monocytes firstly differentiated into macrophages (M0) with phorbol 12-mystrate 13-acetate (PMA). Then, M0 macrophages were polarised in M1 or M2 macrophages using LPS and INFg or IL-4 and IL-13 respectively. Using co-cultures with cancer cells, we investigated the effect of these polarised macrophages on the cancer cell resistance to etoposide.Results and discussionsThe co-culture of macrophages and HepG2 cancer cells reveals that M2 macrophages decreased the etoposide-induced cell death whereas M1 macrophages increased the effects of chemotherapy. These results have been observed by western blot for cleaved Caspase-3 and cleaved PARP-1 and by caspase-3 activity assay in co-culture or by using M2 macrophage conditioned medium. Moreover, a slight chemoresistance was observed in co-culture with unpolarized M0 macrophages. Further investigations revealed that HepG2 cells induced a M0 to M2 polarisation, which seemed to be at the origin of this resistance. The resistance seems to occur by a decrease in DNA damage induction. Furthermore, we showed that M2 conditioned medium increased the expression of cancer stem cell markers by HepG2 cells.ConclusionTaken together, these results show a direct protective effect of M2 macrophages on etoposide induced cell death of HepG2 cancer cells.