Jiyoung Yu (Asan Medical Center)

Kyunggon Kim (University of Ulsan)

Jiyoung Yu (Asan Medical Center)

Kyunggon Kim (University of Ulsan)

Sungryul Yu (Department of Clinical Laboratory Science, Semyung University)

Jung-Yoon Yoo (Department of Biomedical Laboratory Science, Yonsei University Mirae Campus)

Bokyung Kim (University of Ulsan)

Yelin Lee (University of Ulsan)

Jihyeon Kim (University of Ulsan)

Minjoong Kim (University of Ulsan)

Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is largely unknown and a rare subtype of HCC with immune-rich stroma. Tertiary lymphoid structures (TLS), frequently observed in LR-HCC, are known to be prognostically significant in various malignancies; however, their significance in HCC remains unevaluated. Clinicopathologic data of 191 cases of surgically resected conventional HCC (C-HCC, n = 160) and LR-HCC (n = 31) were retrieved. Immunohistochemistry, multiplex immunofluorescence staining, RNA sequencing and proteomic analysis were conducted. Differences between the subtypes were statistically evaluated. LR-HCC demonstrated TLS signatures with significantly higher proteomic-based immune scores in 14 of 17 types of tumour-infiltrating immune cells. Across the global proteome, LR-HCC was well-differentiated from C-HCC and a map of protein-protein interactions between tumour-infiltrating lymphocytes and HCC in tumour microenvironment was completed. LR-HCC is clinicopathologically and molecularly distinct and shows better prognosis compared to C-HCC. Also, the presence of secondary follicle can be an important prognostic marker for better prognosis in both LR-HCC and C-HCC. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. RS-2024-00454407).​