Preoperative Radiomic Approach to Evaluate Tumor-Infiltrating CD8⁺ T Cells in Hepatocellular Carcinoma Patients Using Contrast-Enhanced Computed Tomography.

Abstract

To help identify potential hepatocellular carcinoma (HCC) candidates for immunotherapies, we aimed to develop and validate a radiomics-based biomarker (Rad score) to predict the infiltration of tumor-infiltrating CD8⁺ T cells in HCC patients, and to evaluate the correlation of Rad score with tumor immune characteristics. Overall, 142 HCC patients (n = 100 and n = 42 in the training and validation sets, respectively) were subjected to radiomic feature extraction. Imaging features and immunochemistry data of patients in the training set were subjected to elastic-net regularized regression analysis to predict the level of CD8⁺ T cell infiltration. A Rad score for CD8⁺ T-cell infiltration, which contained seven variables, was developed and was validated in the validation set (area under the curve [AUC]: training set 0.751, 95% confidence interval [CI] 0.656-0.846; validation set 0.705, 95% CI 0.547-0.863). The decision curve indicated the clinical usefulness of the Rad score. A higher Rad score correlated with superior overall and disease-free survival outcomes (p = 0.012 and 0.0088, respectively). Using the pathological slides, we found that the Rad score positively correlated with the percentage of tumor-infiltrating lymphocytes (TILs; Spearman rho = 0.51, p < 0.0001). Moreover, the Rad score could also discriminate inflamed tumors from immune-desert and immune-excluded tumors (Kruskal-Wallis, p < 0.0001), and higher Rad scores could be found in patients with positive programmed cell death ligand 1 expression in tumor/immune cells, as well as those with positive programmed cell death protein 1 expression. The newly developed Rad score was a powerful predictor of CD8⁺ T-cell infiltration, which could be useful in identifying potential HCC patients who can benefit from immunotherapies when validated in large-scale prospective cohorts.