The polarization of immune cells in the tumour environment by TGFβ

Abstract

Transforming growth factor-β (TGFβ) is an immunosuppressive cytokine produced by tumour cells and immune cells that can polarize many arms of the immune system. This Review covers the effects of TGFβ on NK cells, dendritic cells, macrophages, neutrophils, CD8+ and CD4+ effector and regulatory cells, and NKT cells in preclinical animal tumour models and in patients with cancer. Collectively, many recent studies favour the idea that blocking TGFβ signalling in the tumour microenvironment enhances antitumour immunity and may be beneficial for cancer therapy. An overview of the current drugs and reagents for inhibiting TGFβ signalling and their phase in clinical development is also provided.

Tumor Microenvironment and Myeloid-Derived Suppressor Cells

“…Thus, tumor-derived VEGF has been shown to interfere with the proliferation, differentiation and maturation of immature granulocyte-macrophage progenitors, blocking DC maturation and activation as well as inducing the development of immunosuppressive M2 TAMs and their recruitment to the tumor site [63,64]. Acting together with VEGF, accumulated in tumor lesions TGF-β was also able to prevent the DC maturation and to polarize myeloid cells differentiation towards immunosuppressive MDSCs and TAMs in the tumor microenvironment [65].…”

The bright and the dark sides of activin in wound healing and cancer

“…In addition, macrophages and neutrophils change their polarization to a phenotype called N2 (for neutrophils) and M2 (for macrophages). N2 neutrophils and M2 macrophages promote tissue remodelling and angiogenesis, and favour tumour progression (reviewed by Flavell et al, 2010). Neutrophils and macrophages produce large amounts of reactive oxygen and nitrogen species that are not only toxic for invading microorganisms, but also directly damage DNA and modify proteins involved in DNA repair, cell cycle control or apoptosis through covalent modifications of these macromolecules.…”

Microenvironnement tumoral

“…Le TGF- participe à la mise en place de populations immunosuppressives, attire les macrophages dans la tumeur, induit leur polarisation en macrophages de type 2 (immunosuppresseurs) et stimule leur sécrétion de cytokines, dont l'IL-10 et le TGF-. Il est également indispensable à la génération de lymphocytes Tr1 et à la prolifération des Treg [25]. En présence d'IL-6, il polarise les cellules T CD4 naïfs en Th17.…”