Transforming growth factor beta (TGF-β) plays a dual role in tumor initiation and progression, acting as both a tumor suppressor and a promoter. TGF-β exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-β enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines, leading to recruitment and activation of neutrophils with an antitumor phenotype. TGF-β regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor microenvironment, causing direct changes in tumor cells. Understanding TGF-β regulation at the interface of tumor and host immunity provides insights into developing effective TGF-β antagonists and biomarkers for patient selection and treatment efficacy. TGF-β signaling is crucial in tumor initiation and progression. It has three ligands, TGF-β1, TGF-β2, and TGF-β3, with TGF-β1 being the most commonly upregulated in tumor cells. TGF-β signals through type I and type II receptors, leading to phosphorylation of SMAD2 and SMAD3, which enter the nucleus to modulate gene transcription. SMAD7 is a negative regulator of the SMAD signaling pathway. TGF-β also activates non-canonical signaling pathways such as PI3-kinase, p38 kinase, and small GTPase pathways. TGF-β is a tumor suppressor, but mutations in TGF-β receptors or decreased expression can lead to worse prognosis. However, TGF-β is also a tumor promoter, often produced in large quantities by many tumor types and known to be pro-oncogenic. The dual role of TGF-β is complex and involves interactions with various immune cells. TGF-β inhibits immune responses and suppresses anti-tumor immunity. It affects T cells, CD4+ T-cell differentiation, and function, inducing Foxp3 and generating regulatory T cells (Tregs). TGF-β also influences CD8+ T-cell cytotoxicity and NK-cell function. It inhibits NK-cell proliferation and function, which is modulated by CD4+CD25+ regulatory T cells. TGF-β also affects B-cell proliferation and IgA secretion, and plays a role in the development of regulatory B cells (Bregs). TGF-β has a profound impact on the myeloid lineage, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs). These cells contribute to tumor progression and metastasis by promoting angiogenesis, increasing MMPs, and modulating immune responses. TGF-β also regulates the tumor microenvironment, influencing cancer-associated fibroblasts and endothelial progenitor cells. TGF-Transforming growth factor beta (TGF-β) plays a dual role in tumor initiation and progression, acting as both a tumor suppressor and a promoter. TGF-β exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-β enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines, leading to recruitment and activation of neutrophils with an antitumor phenotype. TGF-β regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor microenvironment, causing direct changes in tumor cells. Understanding TGF-β regulation at the interface of tumor and host immunity provides insights into developing effective TGF-β antagonists and biomarkers for patient selection and treatment efficacy. TGF-β signaling is crucial in tumor initiation and progression. It has three ligands, TGF-β1, TGF-β2, and TGF-β3, with TGF-β1 being the most commonly upregulated in tumor cells. TGF-β signals through type I and type II receptors, leading to phosphorylation of SMAD2 and SMAD3, which enter the nucleus to modulate gene transcription. SMAD7 is a negative regulator of the SMAD signaling pathway. TGF-β also activates non-canonical signaling pathways such as PI3-kinase, p38 kinase, and small GTPase pathways. TGF-β is a tumor suppressor, but mutations in TGF-β receptors or decreased expression can lead to worse prognosis. However, TGF-β is also a tumor promoter, often produced in large quantities by many tumor types and known to be pro-oncogenic. The dual role of TGF-β is complex and involves interactions with various immune cells. TGF-β inhibits immune responses and suppresses anti-tumor immunity. It affects T cells, CD4+ T-cell differentiation, and function, inducing Foxp3 and generating regulatory T cells (Tregs). TGF-β also influences CD8+ T-cell cytotoxicity and NK-cell function. It inhibits NK-cell proliferation and function, which is modulated by CD4+CD25+ regulatory T cells. TGF-β also affects B-cell proliferation and IgA secretion, and plays a role in the development of regulatory B cells (Bregs). TGF-β has a profound impact on the myeloid lineage, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs). These cells contribute to tumor progression and metastasis by promoting angiogenesis, increasing MMPs, and modulating immune responses. TGF-β also regulates the tumor microenvironment, influencing cancer-associated fibroblasts and endothelial progenitor cells. TGF-