Researchers at Peking University have uncovered several subtypes in the tumor immune microenvironment (TIME) relevant to liver cancer, according to a study published in Nature this week (title: Liver tumour immune microenvironment subtypes and neutrophil heterogeneity). The research focused on exploring the heterogeneity of the TIME and its impact on tumor metastasis, relapse, and drug resistance.
Study Methodology and Findings
In the study, the researchers performed single-cell RNA-sequencing (scRNA-seq) analysis on 189 samples collected from 124 patients and 8 mice with liver cancer. With over 1 million cells analyzed, they stratified patients into five distinct TIME subtypes, including immune activation, immune suppression mediated by myeloid or stromal cells, immune exclusion, and immune residence phenotypes. Notably, tumor-associated neutrophil (TAN) populations enriched in the myeloid-cell-enriched subtype were associated with an unfavorable prognosis.
Implications for Immunotherapy
Through in vitro induction of TANs and ex vivo analyses of patient TANs, the data showed that CCL4+ TANs can recruit macrophages and that PD-L1+ TANs can suppress T cell cytotoxicity. The study illustrates the diverse subtypes of the liver tumor immune microenvironment, highlights the immunosuppressive functions of TANs, and represents a new potential area for the discovery of immunotherapies targeting TANs.-Fineline Info & Tech
