Transplant - Translational Research Program

Our research utilizes an HCC biomarker panel consisting of alpha-fetoprotein (AFP), Lens culinaris agglutinin fraction of AFP (AFP-L3) and des-gamma-carboxyprothrombin (DCP) to identify aggressive tumor biology in recently diagnosed early-stage HCC. Our research has expanded to include using this biomarker panel as a point assessment of aggressive biology across the spectrum of HCC stages undergoing a variety of treatments including liver-directed therapy (LDT), immunotherapy, or combinations of LDT and immunotherapy. The goal of these studies are to identify a population of patients (i) at risk of rapid tumor progression, (ii) would benefit from more aggressive treatment approach, and (iii) detect minimal residual disease following treatment.

Núñez KG, Sandow T, Burton J, Hibino M, Gimenez J, Cohen A, Mehta N, Thevenot P. Sustained AFP-L3 or DCP Expression is Associated with Progression Risk and Inferior Outcomes in Unresectable Hepatocellular Carcinoma. Clinical Experimental Medicine. 2025 Oct 25;25(1):328.

Núñez KG, Schneider M, Sandow T, Gimenez J, Hibino M, Fort D, Cohen A, Thevenot P. α-Fetoprotein, α-Fetoprotein-L3, and Des-γ-Carboxy Prothrombin Stratify Hepatocellular Carcinoma Treatment Response and Progression Risk. Gastro Hep Adv. 2023 Dec 7;3(3):316-325.

Núñez KG, Sandow T, Fort D, Patel J, Hibino M, Carmody I, Cohen AJ, Thevenot P. Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma. Cancers (Basel). 2021 Sep 23;13(19):4765.

Transarterial radioembolization with Yttrium-90 (⁹⁰Y) is now the most used liver-directed therapy for downstaging HCC patients to liver transplantation. Despite this increased utilization, there is no consensus protocol for ⁹⁰Y within the field of HCC. Our research focuses on understanding how ⁹⁰Y treatment impacts tumor progression rates and overall survival in HCC patients undergoing ⁹⁰Y as a monotherapy or in combination with immunotherapy. The goal of this project is to provide center-specific outcomes data using ablative segmental ⁹⁰Y to treat HCC.

Núñez KG, Hasani N, Burton J, Cronan J, Gimenez J, Sandow T, Cohen A, Thevenot P. Radioembolization (90Y) Achieves Higher Response Rates and Reduces Progression Risk Compared to DEB-TACE in Patient with Hepatocellular Carcinoma. Hepatology Communications. 2026.

Zamani A, Núñez KG, Sandow T, Burton J, Hibino M, Gimenez J, Cohen A, Mehta N, Thevenot P. Single-System Outcomes after Adopting Yttrium-90 Radioembolization with Personalized Dosimetry as the Primary Treatment Approach for Unresectable, Solitary Hepatocellular Carcinoma. ESMO Gastrointestinal Oncology. 2026, 11, 100309.

Núñez KG, Sandow T, Grahovac A, Vallejo-Calzada R, Gimenez J, Bohorquez H, Cohen A, Mizrahi J, Du L, Thevenot P. Contemporary Clinical Utilization of Radioembolization with Immune Checkpoint Inhibitors as First-Line Treatment in HCC: Real-World Report on Safety and Outcomes. Cancers. 2025 Aug 23;17(17):2745.

We are conducting a clinical trial that compares 1-year outcomes in patients with hypoalbuminemia and a new diagnosis of small, early-stage hepatocellular carcinoma (HCC) who are candidates for both 90-Yittrium Therasphere transarterial radioembolization (⁹⁰Y) and microwave ablation (MWA). The study will determine whether treatment with ⁹⁰Y lowers the risk of disease progression within the first year after diagnosis. [NCT05953961]

Núñez KG, Sandow T, Patel J, Hibino M, Fort D, Cohen AJ, Thevenot P. (2022) Hypoalbuminemia Is a Hepatocellular Carcinoma Independent Risk Factor for Tumor Progression in Low-Risk Bridge to Transplant Candidates. Cancers (Basel). 14(7): 1684.

Our work focuses on role and health of lymphocytes (T cells) in HCC patients undergoing liver-directed therapy (LDT). Our work uses flow cytometry and T cell receptor sequencing to study how T cells phenotypes and T cell receptors are altered following LDT. Our goal is to understand how LDT impact T cells.

Núñez KG, Sandow T, Gimenez J, Hibino M, Cohen A, Thevenot P. Yttrium-90 Induces an Effector Memory Response with Neoantigen Clonotype Expansion: Implications for Immunotherapy. Cancer Res Commun. 2024 Aug 1;4(8):2163-2173.

Núñez KG, Sandow T, Lakey MA, Fort D, Cohen AJ, Thevenot PT. Distinct Gene Expression Profiles in Viable Hepatocellular Carcinoma Treated With Liver-Directed Therapy. Front Oncol. 2022 Jun 17;12:809860.

While immunotherapy targeting programmed death-1 (PD-1) in HCC has low response rates (<20%), combining immunotherapy with liver-directed therapies (LDT) is gaining momentum. Our work has identified a patient population with elevated PD-1 expression on circulating T cells with increased risk of tumor progression following treatment. Our goal is to identify a patient population with elevated PD-1 expression that would benefit from anti-PD-1 immunotherapy combined with LDT as a way to improve treatment response rates and outcomes.

Núñez KG, Sandow T, Gimenez J, Hibino M, Fort D, Cohen AJ, Thevenot PT. Lineage-specific regulation of PD-1 expression in early-stage hepatocellular carcinoma following 90yttrium transarterial radioembolization - Implications in treatment outcomes. Eur J Cancer. 2024 Jan;196:113442.

Núñez KG, Sandow T, Fort D, Hibino M, Wright P, Cohen AJ, Thevenot PT. PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival. Cancer Immunol Immunother. 2022 Jun;71(6):1453-1465.