Shunchang Jiao

Despite the crucial involvement of the EGFR pathway in hepatocellular carcinoma (HCC), the clinical efficacy of EGFR antibodies in HCC remains uncertain. W

Background Despite the crucial involvement of the EGFR pathway in hepatocellular carcinoma (HCC), the clinical efficacy of EGFR antibodies in HCC remains uncertain. While existing evidence suggests that immune dysfunction and tumor microenvironment alterations may contribute to treatment resistance, the precise mechanisms underlying this phenomenon in HCC warrant further investigation. Methods In this study, we employed patient-derived xenograft (PDX) models generated from 14 HCC patients enrolled in the REHOPE301 cohort to evaluate the sensitivity to nimotuzumab, a humanized anti-EGFR monoclonal antibody. Whole-exome sequencing (WES) and single-cell RNA sequencing were performed on tumor tissues and tumor-infiltrating lymphocytes (TILs) to elucidate the association between TIL characteristics and EGFR antibody response. A predictive risk score and nomogram were subsequently developed using LASSO regression analysis. The prognostic performance of this model was evaluated using 2 external datasets (ICGC-JP and GSE141202) through receiver operator characteristic (ROC) curves and calibration curves analyses. Results Nimotuzumab demonstrated a 50% response rate (7/14) in PDX models. Immune profiling revealed distinct TIL patterns between responders and non-responders. Notably, CD4 ⁺ CCR7 ⁺ T cells were significantly enriched in resistant tumors (p < 0.001) and negatively correlated with the nimotuzumab response (r = -0.767 p = 0.02). In non-responsive tumors, CD4 ⁺ CCR7 ⁺ T cells exhibited interactions with macrophages and CD8 ⁺ PDCD1 ⁺ T cells. A reduced infiltration of CD4 ⁺ CCR7 ⁺ T cells was associated with improved prognosis and enhanced EGFR antibody efficacy across multiple cancer types. Furthermore, a nine-gene signature related to CD4 ⁺ CCR7 ⁺ T cells was identified as a strong prognostic factor in HCC (HR = 5.19, 95% CI: 3.18–8.46, P < 0.001), and was used to construct a nomogram. WES confirmed prognostic gene mutations (VCAN, CAMK4, and CD226) potentially influencing nimotuzumab response. Conclusions Our findings indicate that increased infiltration of central memory CD4 ⁺ CCR7 ⁺ T cells in HCC may reflect an immunosuppressive tumor microenvironment, thereby impairing EGFR antibody efficacy and worsening patient prognosis.

Background: Immunotherapy has transformed cancer treatment patterns for advanced hepatocellular carcinoma (aHCC) in recent years. Therefore, the identification of predictive biomarkers has important clinical implications. Methods: We collected medical records from 117 aHCC patients treated with anti-PD-1 antibody. Kaplan-Meier analysis and Cox proportional hazard regression were used to evaluate the association between peripheral blood biomarkers and overall survival (OS) and progression-free survival (PFS). Finally, the prognostic nomogram was constructed. Results: The mPFS and mOS were 7.0 months and 18.7 months, respectively. According to Kaplan-Meier analysis and Cox regression analysis, we regarded the treatment regimen (p = 0.020), hemoglobin (Hb) at 6-week (p = 0.042), neutrophil-to-lymphocyte ratio (NLR) at 6-week (p < 0.001), system immune inflammation index (SII) at 6-week (p = 0.125) as predictors of PFS, and alpha fetoprotein (AFP) (p = 0.035), platelet-to-lymphocyte ratio (PLR) (p = 0.012), Hb at 6-week (p = 0.010) and NLR at 6-week (p = 0.020) as predictors of OS. Furthermore, the results suggest that the OS and PFS nomogram model were in agreement with actual observations. Conclusion: Biomarkers in peripheral blood can predict the prognosis of patients with aHCC treated with anti-PD-1 antibody. The development of nomogram models can help us to screen potential patients who can benefit from immunotherapy.

Background: Immunotherapy has transformed cancer treatment patterns for advanced hepatocellular carcinoma (aHCC) in recent years. Therefore, the identification of predictive biomarkers has important clinical implications. Methods: We collected medical records from 117 aHCC patients treated with anti-PD-1 antibody. Kaplan-Meier analysis and Cox proportional hazard regression were used to evaluate the association between peripheral blood biomarkers and overall survival (OS) and progression-free survival (PFS). Finally, the prognostic nomogram was constructed. Results: The mPFS and mOS were 7.0 months and 18.7 months, respectively. According to Kaplan-Meier analysis and Cox regression analysis, we regarded the treatment regimen (p = 0.020), Hb at 6-week (p= 0.042), NLR at 6-week (p < 0.001), SII at 6-week (p = 0.125) as predictors of PFS, and AFP (p = 0.035), PLR (p = 0.012), Hb at 6-week (p = 0.010) and NLR at 6-week (p = 0.020) as predictors of OS. Furthermore, the results suggest that the OS and PFS nomogram model were in agreement with actual observations. Conclusion: Biomarkers in peripheral blood can predict the prognosis of patients with aHCC treated with anti-PD-1 antibody. The development of nomogram models can help us to screen potential patients who can benefit from immunotherapy.