Associations among the mutational landscape, immune microenvironment, and prognosis in Chinese patients with hepatocellular carcinoma

Recent studies suggested that the immune microenvironment and mutational landscape are associated with the response to immune-based therapy in several types of cancer. The roles of those factors in Chinese HCC remain largely unknown. In this study, we obtained 182 FFPE samples of HCC cohort that were previously subjected to NGS (49 WGS, 18 WES, and 115 targeted sequencing). We performed immunohistochemistry to detect CD3, CD4, CD8, CD57, Foxp3, CD68, CD66b, and PD-L1 expression in the samples. We identified diverse associations between the mutational landscape and the immune microenvironment in the HCC samples. High mutational burden and an aristolochic acid-dominated mutational signature were both correlated with elevated tumoral PD-L1 expression and CD3+ T-cell infiltration and high numbers of CD68+ TAMs and CD66b+ TANs. CD4+ and CD8+ T cells exhibited lower infiltration levels in tumors with mutations inAXIN1/CTNNB1and in tumors with aflatoxin-dominant mutational signatures. Moreover, tumors withTP53mutations had less CD8+ T-cell infiltration and more Foxp3+ Treg-cell infiltration than those withoutTP53mutations. Kaplan-Meier survival analysis revealed that the presence of CD8+, Foxp3+, CD66b+, or CD68+ immune cells; tumoral PD-L1 expression alone; or the presence of CD8+ or Foxp3+ cells combined withTP53mutation were predictive of recurrence and poor overall survival after curative resection. In conclusion, the association between the mutational landscape and the immune microenvironment warrants further analysis to determine its impact on patient outcomes to guide personalized immune-based therapy for Chinese patients with HCC.

Automated summary

Recent studies have found various associations between the mutational landscape and the immune microenvironment in HCC patients. High mutational burden and aristolochic acid-dominated mutational signature are correlated with tumoral PD-L1 expression, T-cell infiltration, and the presence of TAMs and TANs. Mutations in certain genes are associated with lower levels of T-cell infiltration in tumors.