Dynamic of peripheral immune signature identified by multiomics and its impact on recurrence after radiofrequency ablation of hepatocellular carcinoma

Kang Li¹Wanting Shi¹Yongjun Li²Yi Song³Baochen Du²Jinxia Guan²Jianjun Li¹Dandan Guo¹Tingting Mei¹Ang Li¹Yonghong Zhang^1*

• ¹Beijing Youan Hospital, Capital Medical University, Beijing, China
• ²BioChain (Beijing) Science and Technology, Inc, Beijing, China
• ³Beijing Friendship Hospital, Capital Medical University, Beijing, China

Background: Radiofrequency ablation (RFA) has emerged as a commonly radical approach for early stage of hepatocellular carcinoma (HCC) patients. Exploring immunity changes after RFA therapy is helpful for reducing recurrence. Methods: In this study, we enrolled 12 patients with HCC with their 47 blood samples including before and after complete RFA therapy. We performed integrative analysis of transcriptome and methylome investigated by a novel self-developed methylation array (HYGEIA panel). Core analyses included differential analyses of both transcriptome and methylome, DIABLO-based multi-omics integration, gene set enrichment analysis, and time-series gene clustering with visualization. Results: Our study elucidated the complex effect of location of CpG sites methylation on their corresponding gene transcription; 58.44% of CpG sites were located in promoter (<=1kb) region and mainly negatively correlated with genes expression. RFA treatment in HCC patients activated antigen processing and presentation and Th1 and Th2 cell differentiation signaling pathways. The anti-tumor immune responses induced by RFA therapy persisted for less than nine months in recurrent patients. Meanwhile, the ability of T cell differentiation in HCC patients was a potential factor to prevent recurrence. Conclusion: These findings elucidated the dynamic peripheral immune remodeling post-RFA and identify host T cell fitness as a key determinant of recurrence, providing a rationale for combining RFA with immunotherapy to prolong protective immune responses.