Host immune and fibroblast pathways

Host immune and fibroblast pathways refer to the complex signaling networks and cellular interactions between the host's immune system and fibroblast populations, particularly within the tumor microenvironment (TME) or fibrotic tissues (Batlle & Massagué, 2019). These pathways are critical in regulating the balance between tissue repair and pathological fibrosis, as well as modulating the immune response against tumors (Sahai et al., 2020). Fibroblasts, especially cancer-associated fibroblasts (CAFs), can secrete factors like TGF-beta and various chemokines that suppress immune cell activity and create a physical barrier of extracellular matrix, leading to therapy resistance (Wynn & Vannella, 2016). Targeting these integrated pathways aims to reprogram the microenvironment to enhance the efficacy of immunotherapies and arrest the progression of fibrotic diseases. Current therapeutic approaches include the use of TGF-beta traps like bintrafusp alfa, small molecule inhibitors of fibroblast activation, and agents that disrupt the recruitment of immunosuppressive cells (NCI, 2023). By modulating these pathways, researchers hope to overcome the 'cold' tumor phenotype and improve outcomes in patients with treatment-resistant cancers and chronic inflammatory conditions.

Other names

Immune-fibroblast axisFibroblast-immune crosstalkTumor microenvironment pathwaysImmune-fibrotic signaling

Inhibition of signaling molecules such as TGF-beta, IL-6, and PDGF that mediate the crosstalk between immune cells and fibroblasts, thereby reducing immunosuppression and pathological extracellular matrix deposition.