Molecular landscape of tumor-associated tissue-resident memory T cells in tumor microenvironment of hepatocellular carcinoma

• DOI: 10.1186/s12964-025-02070-w
• Publication Date: 2025-02-11T17:17:36Z
• Authors: Mi-So Park; Hyeonbin Jo; Hyeree Kim; Ji Young Kim; Woong-Yang Park; Yong-Han Paik; Yeup Yoon; Wonseok Kang; Hong-Hee Won
• Keywords: Tumor Heterogeneity

Immunotherapy for liver cancer is used to rejuvenate tumor-infiltrating lymphocytes by modulating the immune microenvironment. Thus, early protective functions of T cell subtypes with tissue-specific residency have been studied in tumor microenvironment (TME). We identified tumor-associated tissue-resident memory (TA-TRM) cells hepatocellular carcinoma (HCC) and characterized their molecular signatures. obtained single-cell RNA TCR sequencing data from five patients HCC. The heterogeneous characteristics TRM subsets within TME were then investigated validated. Risk scores calculated survival analysis using significant core marker genes based on Cancer Genome Atlas International Consortium. signaling pathways, trajectories, clonal diversity TA-TRM investigated. two clusters (CD69+ CD103+) that expressed unique signature validated similar patterns an independent dataset. gene expression associated both datasets. Trajectory revealed lineages followed different trajectory paths distinct across pseudo-time. CD103+ showed diverse clonotypes shared other groups. Lower interactions observed recurrent than non-recurrent samples. CXCL13-CXCR3 interaction between regulatory was only HCC demonstrated signatures, relevance survival, networks according recurrence. study findings provide a better understanding potential immunotherapeutic strategies.