Understanding the role of HSF1 in pro tumorigenic reprogramming of macrophages in cancer

The tumor microenvironment (TME) is a complex biological system of cells and extracellular proteins that support tumor formation and progression. Tumor associated macrophages (TAMs) are prominent components of the immune tumor microenvironment. Their presence is associated with poor prognosis as they were found to have pro-tumoral functions such as angiogenesis, remodeling of the extracellular matrix to aid invasion, motility, intravasation and immunosuppression. In the tumor, most macrophages display an anti-inflammatory (M2-like) polarization state, suggesting that signals from the TME inflict a switch process that promotes a tumor supporting phenotype in these cells. This tumor supporting reprogramming process occurs in most TME cell types and the pathways responsible for it are not yet fully understood. We have recently shown that transcriptional reprogramming of fibroblasts into cancerassociated fibroblasts is mediated by the heat shock factor 1 (HSF1) transcription factor. HSF1 is a proteotoxic stress master regulator, and was shown to be an important player in the support of cancer cell survival and malignancy. Here we hypothesize that HSF1 may also play a complementary tumor-promoting role in tumor associated macrophages (TAMs). Using invitro and in-vivo models, we found different gene signatures between HSF1 WT macrophages and HSF1 null macrophages. Consequently, HSF1 might have an important role in macrophages polarization towards a tumor supporting state.