# Immunoscore Predicted by Dynamic Contrast-Enhanced Computed Tomography Can Be a Non-Invasive Biomarker for Immunotherapy Susceptibility of Hepatocellular Carcinoma

## TL;DR

This study shows that CT scans can predict which liver cancer patients are likely to benefit from immunotherapy based on tumor imaging features.

## Contribution

The study introduces peritumoral arterial phase enhancement on CT scans as a non-invasive biomarker for immunotherapy response in hepatocellular carcinoma.

## Key findings

- Peritumoral enhancement in the arterial phase correlates with higher immunoscores in hepatocellular carcinoma.
- Tumors with arterial phase enhancement show significantly longer time to progression during immunotherapy.
- Dynamic contrast-enhanced CT can non-invasively predict immunotherapy susceptibility in HCC patients.

## Abstract

Immunotherapy is the core treatment for hepatocellular carcinoma; however, the therapeutic efficacy is heterogeneous due to varying tumor immune microenvironments. This study aimed to noninvasively identify tumors that are more likely to benefit from immunotherapy by assessing the immune microenvironment of surgical resection sections and contrasting them with easily accessible CT findings. The results of this study showed that masses with peritumoral enhancement in the arterial phase have a higher immunoscore and are more likely to be susceptible to immunotherapy, which has a significant impact on clinical practice.

Background/Objectives: Although immunotherapy is the primary treatment option for intermediate-stage hepatocellular carcinoma (HCC), its efficacy varies. This study aimed to identify non-invasive imaging biomarkers predictive of the immunoscore linked to dynamic contrast-enhanced computed tomography (CECT). Methods: We performed immunohistochemical staining with CD3+ and CD8+ antibodies and counted the positive cells in the invasive margin (IM) and central tumor (CT), converting them to an immunoscore of 0 to 4 points. We assessed the dynamic CECT findings obtained from 96 patients who underwent hepatectomy for HCC and evaluated the relationship between dynamic CECT findings and immunoscores. For validation, we assessed the treatment effects on 81 nodules using the Response Evaluation Criteria in Solid Tumors in another cohort of 41 patients who received combined immunotherapy with atezolizumab and bevacizumab (n = 27) and durvalumab and tremelizumab (n = 14). Results: HCCs with peritumoral enhancement in the arterial phase (p < 0.001) and rim APHE (p = 0.009) were associated with the immunoscore in univariate linear regression analysis and peritumoral enhancement in the arterial phase (p = 0.004) in multivariate linear regression analysis. The time to nodular progression in HCCs with peritumoral enhancement in the arterial phase was significantly longer than that in HCCs without this feature (p < 0.001). Conclusions: We identified HCCs with peritumoral enhancement in the arterial phase as a noninvasive imaging biomarker to predict immune-inflamed HCC with a high immunoscore tendency. These HCCs were most likely to respond to combined immunotherapy.