TGFβ and the Tumor Microenvironment in Colorectal Cancer

Abstract

Growing evidence supports an important role of the tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC). Resident cells such as fibroblasts or immune cells infiltrating into the TME maintain continuous crosstalk with cancer cells and thereby regulate CRC progression. One of the most important molecules involved is the immunoregulatory cytokine transforming growth factor-β (TGFβ). TGFβ is released by various cells in the TME, including macrophages and fibroblasts, and it modulates cancer cell growth, differentiation, and cell death. Mutations in components of the TGF pathway, including TGFβ receptor type 2 or SMAD4, are among the most frequently detected mutations in CRC and have been associated with the clinical course of disease. Within this review, we will discuss our current understanding about the role of TGFβ in the pathogenesis of CRC. This includes novel data on the molecular mechanisms of TGFβ signaling in TME, as well as possible strategies for CRC therapy targeting the TGFβ pathway, including potential combinations with immune checkpoint inhibitors.

Global trends in tumor microenvironment-related research on tumor vaccine: a review and bibliometric analysis

“…Modulating the recruitment, expansion, activation, and immunosuppression of MDSCs has the potential to partially reinstate the body’s ability to mount an effective antitumor immune response ( 70 ). TGFβ not only exerts anti-tumor activity in premalignant cells by inducing apoptosis or cell cycle blockade, but also promotes tumor-promoted polarization of innate immune cells or cancer-associated fibroblasts ( 71 ). There is an increasing amount of data indicating the pleiotropic nature of TGF-β signaling as a crucial pathway in the development of a fibrotic TME.…”