Background and Aims: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC. Approach and Results: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels (p<0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68⁺ cells from patients with high serum IgA levels (p<0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs (p<0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8⁺ T cells. Interestingly, activated CD8⁺ T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs (p<0.05). Conclusions: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.

This study aimed to determine the association between serum D-dimer levels and the risk of acute kidney injury (AKI) in patients undergoing living donor liver transplantation (LDLT). Clinical data of 675 patients undergoing LDLT were retrospectively analyzed. The exclusion criteria included a history of kidney dysfunction, emergency cases, and missing data. The final study population of 617 patients was divided into the normal and high D-dimer groups (cutoff: 0.5 mg/L). After LDLT, 145 patients (23.5%) developed AKI. A high D-dimer level (>0.5 mg/L) was an independent predictor of postoperative development of AKI in the multivariate analysis when combined with diabetes mellitus [DM], platelet count, and hourly urine output. AKI was significantly higher in the high D-dimer group than in the normal D-dimer group (odds ratio [OR], 2.792; 95% confidence interval [CI], 1.227–6.353). Patients with a high D-dimer exhibited a higher incidence of early allograft dysfunction, longer intensive care unit stay, and a higher mortality rate. These results could improve the risk stratification of postoperative AKI development by encouraging the determination of preoperative D-dimer levels in patients undergoing LDLT.

Park SE, et al. Ann Surg Treat Res. 2021 Jun;100(6):329-337. https://doi.org/10.4174/astr.2021.100.6.329

Sun WY, et al. J Breast Cancer. 2025 Mar;28:e11. https://doi.org/10.4048/jbc.2024.0262

Background/Aim: Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated.Methods: Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay.Results: CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2.Conclusions: CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.