Background: Tumor-infiltrating leukocytes (TILs) are immune cells surrounding tumor cells, and several studies have shown that TILs are potential survival predictors in different cancers. However, few studies have dissected the differences between hepatitis B- and hepatitis C-related hepatocellular carcinoma (HBV−HCC and HCV−HCC). Therefore, we aimed to determine whether the abundance and composition of TILs are potential predictors for survival outcomes in HCC and which TILs are the most significant predictors. Methods: Two bioinformatics algorithms, ESTIMATE and CIBERSORT, were utilized to analyze the gene expression profiles from 6 datasets, from which the abundance of corresponding TILs was inferred. The ESTIMATE algorithm examined the overall abundance of TILs, whereas the CIBERSORT algorithm reported the relative abundance of 22 different TILs. Both HBV−HCC and HCV−HCC were analyzed. Results: The results indicated that the total abundance of TILs was higher in non-tumor tissue regardless of the HCC type. Alternatively, the specific TILs associated with overall survival (OS) and recurrence-free survival (RFS) varied between subtypes. For example, in HBV−HCC, plasma cells (hazard ratio [HR] = 1.05; 95% CI 1.00–1.10; p = 0.034) and activated dendritic cells (HR = 1.08; 95% CI 1.01–1.17; p = 0.03) were significantly associated with OS, whereas in HCV−HCC, monocytes (HR = 1.21) were significantly associated with OS. Furthermore, for RFS, CD8+ T cells (HR = 0.98) and M0 macrophages (HR = 1.02) were potential biomarkers in HBV−HCC, whereas neutrophils (HR = 1.01) were an independent predictor in HCV−HCC. Lastly, in both HBV−HCC and HCV−HCC, CD8+ T cells (HR = 0.97) and activated dendritic cells (HR = 1.09) had a significant association with OS, while γ delta T cells (HR = 1.04), monocytes (HR = 1.05), M0 macrophages (HR = 1.04), M1 macrophages (HR = 1.02), and activated dendritic cells (HR = 1.15) were highly associated with RFS. Conclusions: These findings demonstrated that TILs are potential survival predictors in HCC and different kinds of TILs are observed according to the virus type. Therefore, further investigations are warranted to elucidate the role of TILs in HCC, which may improve immunotherapy outcomes.

Coronavirus disease 2019 (COVID-19) remains a public health concern even after its pandemic status officially ended on May 5, 2023, when XBB became the globally predominant SARS-CoV-2 variant. Amid population immunity, the benefit of the monovalent XBB.1.5 vaccines remains uncertain. This systematic review searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials through November 30, 2024, for studies evaluating the effectiveness of XBB.1.5 vaccines in adults during the 2023-2024 season. Meta-analyses were conducted using a random-effects model (PROSPERO registration: CRD42024513730). Twenty-one eligible studies, with a total of 53,396,781 participants, were included. Vaccine effectiveness (VE) in the first month post-vaccination was 52.9 % (95 % CI: 47.6 %-57.6 %) against SARS-CoV-2 infection, 64.4 % (95 % CI: 59.3 %-68.9 %) against COVID-19-related hospitalization, and 77.3 % (95 % CI: 67.1 %-84.3 %) against COVID-19-related death. However, by the fifth month, VE declined to 26.7 %, 52.3 %, and 69.4 %, respectively. Notably, against the JN.1 variant that replaced XBB in December 2023, VE against infection, hospitalization, and death dropped significantly by 47 % (from 53.7 % to 28.3 %), 32 % (from 67.8 % to 46.2 %), and 26 % (from 77.3 % to 57.1 %), respectively. VE against hospitalization in individuals aged >60 years was not inferior to that in those aged <60 years (57.2 % versus 49.2 %; subgroup difference, p = 0.24). XBB.1.5 vaccines provided substantial protection against severe COVID-19 outcomes in the 2023-2024 season prior to the emergence of the JN.1 variant. These findings underscore the need for updated COVID-19 vaccinations to maintain protection against evolving SARS-CoV-2 variants.