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Simple Summary: A reliable efficacy predictor for immunotherapy is warranted due to its unsatisfying responsive rate among cancer patients. Endonuclease VIII-like protein 3 (NEIL3) is a DNA glycosylase reported to be heightened in specific cancers. However, little is known regarding the immunological features of NEIL3 among cancers. Here, a pan-cancer landscape was presented to elucidate the characteristics of NEIL3 in the tumor microenvironment (TME). In this study, we demonstrated that NEIL3 may be a promising indicator for tumor prognosis, immunotherapy, and chemotherapy. With the aim of enhancing the understanding of NEIL3 in prognosis prediction and therapy administration, we conducted a pan-cancer landscape analysis on NEIL3. The mutation characteristics, survival patterns, and immune features of NEIL3 across cancers were analyzed. Western blotting, qPCR, and immunohistochemistry were conducted to validate the bioinformatics results. The correlation between NEIL3 and chemotherapeutic drugs, as well as immunotherapies, was estimated. NEIL3 was identified as an oncogene with prognostic value in predicting clinical outcomes in multiple cancers. Combined with the neoantigen, tumor mutational burden (TMB), and microsatellite instability (MSI) results, a strong relationship between NEIL3 and the TME was observed. NEIL3 was demonstrated to be closely associated with multiple immune parameters, including infiltrating immunocytes and pro-inflammatory chemokines, which was verified by experiments. More importantly, patients with a higher expression of NEIL3 were revealed to be more sensitive to chemotherapeutic regimens and immune checkpoint inhibitors in selected cancers, implying that NEIL3 may be an indicator for therapeutic administration. Our study indicated NEIL3 has a strong association with the immune microenvironment and phenotypic changes in certain types of cancers, which facilitated the improved understanding of NEIL3 across cancers and highlighted the potential for clinical application of NEIL3 in precision medical stratification. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatitis B virus (HBV) load and antigens are related to the innate and adaptive immunity of chronic hepatitis B (CHB) patients. As a new HBV biomarker, the role of pregenomic RNA (pgRNA) in host immunity is not known. This study aimed to identify the relationship between serum HBV pgRNA and host immunity in CHB patients. Methods: Two hundred twenty‐five treatment‐naïve CHB patients were enrolled. Serum cytokines were measured by cytokine antibody array (Luminex multiplex platform). Th1 (T‐helper cell, Th) and Th2 cells were tested by flow cytometry. Serum HBV pgRNA was detected by a reverse transcription‐polymerase chain reaction. Results: Serum HBV pgRNA was significantly different among patients in different disease phases and significantly associated with both HBV antigens and antibodies. Serum HBV pgRNA was positively correlated with the HBsAg level (P <.001) and the presence of HBeAg (P <.001). Patients with higher HBcAb levels showed lower serum HBV pgRNA levels (P =.003). Notably, HBsAb positivity was associated with higher levels of serum HBV pgRNA in HBeAg(−) patients (P =.049). Serum HBV pgRNA was positively associated with ALT level, Th2 cell frequency, and related cytokine sCD30 (P <.001, P <.001, and P =.003, respectively), but negatively associated with Th1‐related cytokine interleukin (IL)‐12P70 and cytotoxic lymphocytes (CTLs) (P =.017 and P <.001, respectively). Conclusion: Our study confirmed the relationship between serum HBV pgRNA and host immunity. The results demonstrated that serum HBV pgRNA is positively correlated with Th2 immunity but negatively correlated with Th1 immunity, indicating that it might have a relationship with HBV antigen conversion and CTL immunodeficiency in CHB patients. Highlights: Serum HBV pgRNA had a relationship with host immunity.Serum HBV pgRNA was positively correlated with Th2 cells and cytokines.Serum HBV pgRNA was negatively correlated with CTLs and Th1 cytokine. [ABSTRACT FROM AUTHOR]

To the Editor: Severe acute respiratory syndrome (SARS) is a recently recognized infectious disease caused by a novel human coronavirus (SARS-CoV) (1). The first case of SARS, diagnosed as communicable [...]

Background: There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity.Methods: A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines. Peripheral blood mononuclear cells from patients and healthy controls were tested for NK cell frequency, phenotype and function using flow cytometry.Results: A significant decrease in activating receptor NKp44 and NKp46 expression and significant increase of exhaustion molecule Tim-3 expression were observed in NK cells from CHB patients. Reduced cytokine secretion and preserved or elevated cytotoxic function were also observed. Patients in the IT group exhibited comparable cytokine secretion and cytolytic capacity as age-matched IA patients. NK cell anti-viral functions were preserved in GZ patients. Some of the NK cell function in patients who were excluded from treatment by the current treatment guidelines was less compromised than patients who qualified for treatment.Conclusion: Our findings provide evidence of veritable NK cell immunity during different natural history phases in treatment-naïve patients with chronic HBV Infection. Chronic HBV infection hindered NK cell function in CHB patients. However, the presumed IT and GZ statuses of CHB patients based on the clinical parameters may not accurately reflect the inner immune status of these patients and should be reconsidered. Some patients excluded from treatment by the current treatment guidelines may be able to be selected as candidates for treatment. [ABSTRACT FROM AUTHOR]

Background: Fatty acid binding protein 1 (FABP1), a low molecular weight intracellular protein, has been proposed as a potential useful serum biomarker for liver injury. However, limited investigations have been conducted in chronic hepatitis B virus (HBV)-related liver disease., Objective: To investigate the diagnostic potential of FABP1 in disease progression among patients with chronic HBV-related liver disease., Methods: A prospective study was conducted on 293 patients with chronic HBV-related liver diseases, including chronic asymptomatic carrier (ASC), chronic hepatitis B (CHB). FABP1 was measured in serum samples collected at admission and some selected liver biopsies., Results: Immunohistochemical analysis revealed abundant cytoplasmic expression of FABP1 in hepatocytes. A significant negative correlation was observed between FABP1 expression and inflammation grades in liver tissue (Spearman's r = -0.355, P = 0.017). However, no statistically significant correlation was found with fibrosis (P > 0.05). Serum FABP1 levels in the case group were significantly higher than in the healthy control (HC) group [median: 804.2 (687.8, 939.2) vs. 709.1 (626.2, 807.8) ng/ml, Z = -5.505, P < 0.001] and showed correlations with alanine aminotransferase (ALT), aspartate aminotransferase (AST); total bilirubin (TBIL); direct bilirubin (DBIL); albumin (ALB), etc. Its levels progressively increased with the advancement from ASC to CHB, with significant differences compared to the HC group (P < 0.001), especially in ASC patients with high HBV DNA (exceeding 10 6  IU/ml, P = 0.019), HBeAg positive (P = 0.013) and ALT higher than 0.5 times upper limit of normal (ULN)(P = 0.035). Meanwhile, serum FABP1 in CHB patients with higher TBIL(P = 0.005) or the severe CHB were higher (P = 0.002)., Conclusion: Our study demonstrated a significant inverse correlation between FABP1 levels and the severity of inflammation grades in patients with HBV-related liver diseases. Furthermore, elevated serum FABP1 levels were observed in these patients, suggesting its potential as a biomarker for assessing HBV-related liver damage to initiate antiviral therapy. Additionally, further evaluation is required to determine its potential as a biomarker for assessing disease severity., (© 2024. The Author(s).)