Transforming Growth Factor-β: A Multifunctional Regulator of Cancer Immunity

SIMPLE SUMMARY: Transforming growth factor beta (TGF-β) is a multifunctional cytokine that can restrict cancer onset but also promote cancer progression at late stages of cancer. The ability of TGF-β in producing diverse and sometimes opposing effects relies on its potential to control different cellular signalling and gene expression in distinct cell types, and environmental settings. The tumour promoting role of TGF-β is primarily mediated through its effects on the local tumour microenvironment (TME) of the cancer cells. In this review, we discuss the most recent research on the role and regulation of TGF-β, with a specific focus on its functions on promoting cancer progression through targeting different immune cells in the TME as well as its therapeutic perspectives. ABSTRACT: Transforming growth factor-β (TGF-β) was originally identified as an anti-tumour cytokine. However, there is increasing evidence that it has important roles in the tumour microenvironment (TME) in facilitating cancer progression. TGF-β actively shapes the TME via modulating the host immunity. These actions are highly cell-type specific and complicated, involving both canonical and non-canonical pathways. In this review, we systemically update how TGF-β signalling acts as a checkpoint regulator for cancer immunomodulation. A better appreciation of the underlying pathogenic mechanisms at the molecular level can lead to the discovery of novel and more effective therapeutic strategies for cancer.