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TGF-beta is a key regulator of immune responses, inflammation and cancer. In addition to the well-established effects of TGF-beta on CD4+ T cell differentiation and reprogramming, TGF-beta also plays critical roles in other immune cells. TGF-beta has also been implicated in the regulation of the interactions among immune cells, microbiota and epithelial cells. In addition to safeguarding immune homeostasis and suppressing chronic inflammation and autoimmunity, TGF-beta is emerging as a potential checkpoint in anti-tumor immunity. Despite great progress in the field, key questions related to TGF-beta functions in immune responses are still largely undetermined. Therefore, it is imperative to understand the cellular and molecular mechanisms by which TGF-beta controls such diverse immune cells. Elucidation of these pathways would allow us to understand the pathogenesis of chronic inflammation, autoimmunity and cancer and aid development of therapeutic practices in experimental and ultimately clinical settings. This meeting will gather together experts in the fields of both TGF-beta signaling and immunology to discuss new findings and update the pivotal role of TGF-beta in immunity, inflammation and cancer, with the aim to lay out the critical and key questions and outline new directions.