Department of Internal Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Deutsches Zentrum Immuntherapie, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Cells. 2023 Apr 12;12(8):1139. doi: 10.3390/cells12081139.
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.
越来越多的证据支持肿瘤微环境（TME）在结直肠癌（CRC）发病机制中的重要作用。浸润到 TME 中的常驻细胞，如成纤维细胞或免疫细胞，与癌细胞保持持续的相互作用，从而调节 CRC 的进展。其中最重要的分子之一是免疫调节细胞因子转化生长因子-β（TGFβ）。TGFβ由 TME 中的各种细胞释放，包括巨噬细胞和成纤维细胞，它调节癌细胞的生长、分化和细胞死亡。TGF 通路成分的突变，包括 TGFβ 受体 2 型或 SMAD4，是 CRC 中最常检测到的突变之一，并与疾病的临床过程相关。在这篇综述中，我们将讨论我们目前对 TGFβ在 CRC 发病机制中的作用的理解。这包括 TGFβ信号在 TME 中的分子机制的新数据，以及针对 TGFβ 通路的 CRC 治疗的可能策略，包括与免疫检查点抑制剂的潜在组合。
