2024/11/02 by Jia Ming Nickolas Teo, Zhulin Chen, Weixin Chen +15 · 1 voice · 1 citation
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Immune cells in cancer #Single-cell and spatial transcriptomics #Immune Cell Function and Interaction
paper · pdf · doi:10.1084/jem.20241442
openalex publication_date 2024/11/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Tumor-associated neutrophils (TANs) are heterogeneous; thus, their roles in tumor development could vary depending on the cancer type. Here, we showed that TANs affect metabolic dysfunction-associated steatohepatitis hepatocellular carcinoma (MASH-related HCC) more than viral-associated HCC. We attributed this difference to the predominance of SiglecFhi TANs in MASH-related HCC tumors. Linoleic acid and GM-CSF, which are commonly elevated in the MASH-related HCC microenvironment, fostered the development of this c-Myc-driven TAN subset. Through TGFβ secretion, SiglecFhi TANs promoted HCC stemness, proliferation, and migration. Importantly, SiglecFhi TANs supported immune evasion by directly suppressing the antigen presentation machinery of tumor cells. SiglecFhi TAN removal increased the immunogenicity of a MASH-related HCC model and sensitized it to immunotherapy. Likewise, a high SiglecFhi TAN signature was associated with poor prognosis and immunotherapy resistance in HCC patients. Overall, our study highlights the importance of understanding TAN heterogeneity in cancer to improve therapeutic development.