A Noninvasive Approach to Evaluate Tumor Immune Microenvironment and Predict Outcomes in Hepatocellular Carcinoma

It is widely recognized that tumor immune microenvironment (TIME) plays a crucial role in tumor progression, metastasis, and therapeutic response. Despite several noninvasive strategies have emerged for cancer diagnosis and prognosis, there are still lack of effective radiomic-based model to evaluate TIME status, let alone predict clinical outcome and immune checkpoint inhibitor (ICIs) response for hepatocellular carcinoma (HCC). In this study, we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response. A total of 301 patients who underwent magnetic resonance imaging (MRI) examinations were enrolled in our study. The intra-tumoral expression of 17 immune-related molecules were evaluated using co-detection by indexing (CODEX) technology, and we construct Immunoscore (IS) with the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression method to evaluate TIME. Of 6115 features extracted from MRI, five core features were filtered out, and the Radiomic Immunoscore (RIS) showed high accuracy in predicting TIME status in testing cohort (area under the curve = 0.753). More importantly, RIS model showed the capability of predicting therapeutic response to anti-programmed cell death 1 (PD-1) immunotherapy in an independent cohort with advanced HCC patients (area under the curve = 0.731). In comparison with previously radiomic-based models, our integrated RIS model exhibits not only higher accuracy in predicting prognosis but also the potential guiding significance to HCC immunotherapy.