The mechanism by which tertiary lymphoid structures in tumours affect prognosis and immunotherapy in patients with hepatocellular carcinoma

Abstract

Background Tertiary lymphoid structures (TLSs) are formed by the aggregation of tumour-infiltrating lymphocytes (TILs), which is driven by chemokines or cytokines in the tumour microenvironment. Studies have shown that TLSs are associated with good prognosis in patients with various solid tumours and can improve patient responses to immunotherapy. However, the role of TLSs in hepatocellular carcinoma (HCC) remains controversial, and the underlying molecular mechanism is unclear. Methods According to haematoxylin-eosin (HE) staining results, 150 HCC patients from Xijing Hospital were divided into TLS + and TLS- groups, and Kaplan–Meier (K-M) analysis was performed to assess their overall survival (OS) and recurrence-free survival (RFS). Spearman correlation analysis was used to calculate the correlation between LCK and TILs, and the molecular pathways of LCK regulating immunotherapy were clarified through enrichment analysis. Immune score was calculated based on the expression difference of LCK to evaluate the sensitivity of HCC patients to ICIs. Results The HE results showed that 61 (40.7%) of 150 HCC patients had TLSs, and 89 (59.3%) didn't. The K-M results showed that TLSs had no effect on the OS of HCC patients but significantly affected the RFS. Enrichment analysis showed that upregulation of LCK expression mainly regulated cytokine signalling pathway, the chemokine signalling pathway and T cell activation. Immune score showed that HCC patients with high expression of LCK had higher sensitivity to ICIs. Conclusion LCK may regulate the sensitivity of HCC patients to ICIs by affecting the related pathways of TLSs formation to improve the prognosis of patients.