Your Donations in Action: Yu-Hui Huang, MD

Levels of Tumor-Infiltrating Lymphocytes in Patients with Advanced Stage Hepatoceullular Carcinoma


Levels of tumor-infiltrating lymphocytes (TILs) in the hepatocellular carcinoma (HCC) microenvironment have been correlated with prognosis in patients with early-stage HCC following surgical resection, but levels in patients with more advanced stage or infiltrative disease, and its association with outcomes after locoregional therapy (LRT), have not been characterized. In HCC, infiltration of T-cell subpopulations into the tumor microenvironment reflects the host immune response and may impact prognosis.

2018 RSNA Research Medical Student Grant recipient, Yu-Hui Huang, MD, University of Minnesota, Minneapolis, investigated “Characterizing Associations Between T-cell Populations in Hepatocellular Carcinoma and Clinicopathological Features and Outcomes,” which aimed to quantify tumoral and peritumoral T-cells and, in doing so, assess their association with baseline features and LRT outcomes.

The retrospective study included 35 patients with 36 biopsyproven HCC that spanned all Barcelona clinic liver cancer (BCLC) stages and underwent LRT of transcatheter arterial chemoembolization (TACE), thermal ablation, Y90 radioembolization or combined TACE/ablation. Multiplex immunohistochemistry was performed on formalin-fixed biopsy specimens. Antibodies targeted CD3, CD8, CD4, FOXP3, CD45RO, and Glypican-3/Arginase-1. T-cells were defined as cytotoxic, helper, regulatory or regulatory memory T-cells. T-cells in tumor and peritumoral tissue were quantified.

Associations between high (above median) T-cell density, baseline features and transplantfree survival were assessed with univariate logistic regression and Cox proportional hazard models. Dr. Huang and her team found that HCCs with high intratumoral helper T-cell density were less likely to exceed 5 cm. Patients with high intratumoral cytotoxic T-cell density had reduced odds of exceeding Milan criteria. Patients with elevated intratumoral regulatory T-cells were less likely to have BCLC B-D disease. High peritumoral cytotoxic T-cell density was associated with reduced transplant-free survival.

“Our study showed that tumor infiltrating helper, cytotoxic and regulatory T-cells were seen in smaller, early-stage tumors and may inhibit HCC growth, while peritumoral cytotoxic T-cells were associated with reduced transplant-free survival,” Dr. Huang said. “T-cell subpopulations may therefore impart prognostic information and provide opportunities for targeted therapy.”