Figure 1. Impacts of CRLM on the hepatic immune microenvironment. Legend: Tumoural cells release exosomes that facilitate angiogenesis and enhance endothelial permeability. These exosomes also interact with KCs, prompting a shift towards a proinflammatory M2 phenotype and inducing apoptosis in NK cells and cytotoxic CD8+ T cells. The M2 macrophages, in turn, release TGF-beta, contributing to the differentiation of physiological HSCs into CAFs. Additionally, M2 macrophages downregulate ANGPTL1, resulting in heightened vascular permeability. Both N1 and N2 neutrophils stimulate VEGF production, thereby increasing angiogenesis. Furthermore, N2 and M2 cells secrete cytokines with immunosuppressive properties. These intricate interactions collectively contribute to a decline in CD8+ T cells and an elevation in Tregs, culminating in an augmented expression of TIM-3. Activation of TIM-3 induces dysfunction in NK cells and facilitates the transition of macrophages to the M2 phenotype, thereby perpetuating tumour progression and immunosuppression. N1, Neutrophil type 1; N2, Neutrophil type 2; KC, Kupffer cell; M1, Macrophage type 1; M2, Macrophage type 2; TGF-beta, Transforming growing factor beta; VEGF, Vascular endothelial growing factor; HSC, Hepatic stellate cell; CAF, Cancer-associated fibroblast; NK, Natural killer cell; TIM-3, T-cell immunoglobulin mucin 3.