脂肪性肝炎改变淋巴细胞细胞毒性和定位，加速结直肠癌肝转移

High-fat diet (HFD) and Western diet (WD), were used to create MAFLD and MASH respectively. MC38 cancer cells were injected intrasplenically to create CRLM model. Single-cell RNA sequencing (scRNA-seq), RT-PCR and immunohistology were used to study hepatic immune-cell composition, phenotypes, and localization.

Both diets significantly increased CRLM establishment, while only WD altered hepatic inflammation. The WD-promotes IL-10 and TGF-β1 elevation, an anti-inflammatory cytokines, inhibiting cytotoxic CD8 + T cells and NK cells and supporting an immunosuppressive environment. Although MASH led to an increased presence of hepatic CD8 + and NK cells, their infiltration into metastatic foci was reduced and was associated with a decrease in expression of cytotoxic markers. In our murine model of MASH, CD8 + T-cell depletion reduced the number of CRLM foci, which was accompanied by a decrease in IFN-γ-associated cytokines and a significant increase in the infiltration of granzyme-B expressing NK cells, ultimately enhancing cytotoxic killing ability.

This research underscores the crucial influence of diet-induced immune changes on CRLM establishment and progression. It illustrates that the co-localization of immune cells within liver metastases significantly affects their functionality, highlighting potential therapeutic strategies to balance immune exhaustion and activation.