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Increased Regulatory T-cells in Tumor Microenvironment is Associated with Hepatocellular Carcinoma Differentiation in Patients Undergoing Liver Transplantation

G. Orozco1, R. Gedaly2, L. Turcios2, F. Marti2

1Surgery, University of Kentucky, Lexington, KY, 2UKHC, Lexington, KY

Meeting: 2022 American Transplant Congress

Abstract number: 35

Keywords: Hepatocellular carcinoma, Malignancy, T cells

Topic: Clinical Science » Liver » 56 - Liver: Hepatocellular Carcinoma and Other Malignancies

Session Information

Session Name: Hepatocellular Carcinoma and Other Malignancies

Session Type: Rapid Fire Oral Abstract

Date: Sunday, June 5, 2022

Session Time: 3:30pm-5:00pm

 Presentation Time: 4:00pm-4:10pm

Location: Hynes Room 312

*Purpose: Tumor-infiltrating lymphocytes are an essential component of the tumor microenvironment. The balance between cytotoxic effector T cells and immunosuppressive regulatory T cells is critical in the immune response against cancer cells and it is regarded as possible target for immunotherapy in hepatocellular carcinoma (HCC).

*Methods: We analyzed a retrospective cohort of 165 patients with HCC who underwent liver transplantation (LT) at our institution between 1998 and 2016. Explanted livers were analyzed for tumor size, number of lesions, differentiation, lymph node invasion, capsular invasion, and microvascular invasion as main endpoints. Immunohistochemistry staining was used to identify tumor-infiltrating lymphocytes and regulatory T cells. Backward stepwise regression analyses were performed to correlate regulatory T-cell counts, significant clinical, pathological and laboratory data with the main outcomes. In an HCC animal model, we investigated the in vivo anti-tumor effect of 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535). We also analyzed the immunomodulatory properties of FH535 on primary human effector and regulatory T-cells.

*Results: In this cohort of HCC patients, 55.2% had HCV infection and 39.4% alcohol-related liver disease. The median tumor size was 2.2 cm, 15% of patients had microvascular invasion, and 24.8% had poorly differentiated HCC. TIL-Treg counts were independently associated with poorly differentiated HCC (OR, 0.75; 95% CI: 0.57-0.99; p=0.046). We demonstrated a strong positive correlation between tumor differentiation and TIL-Treg cells count (AUC: 0.776, 95% CI 0.647-0.904). In the animal model, mice treated with FH535 had significantly reduced tumor volume (67% reduction after 10-day treatment compared to untreated animals, p<0.05) and tumor weight (42% reduction, p< 0.001). Flow cytometry analyses in primary human T lymphocytes demonstrated the preferential inhibition of regulatory T-cell function by FH535.

*Conclusions: Increased intratumoral regulatory T-cell count is associated with poorly differentiated HCC in patients undergoing LT. Here, we proposed that the disruption of the regulatory T cell function induced by FH535 has an immunomodulatory effect that might contribute to its anti-neoplastic properties in HCC.

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To cite this abstract in AMA style:

Orozco G, Gedaly R, Turcios L, Marti F. Increased Regulatory T-cells in Tumor Microenvironment is Associated with Hepatocellular Carcinoma Differentiation in Patients Undergoing Liver Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/increased-regulatory-t-cells-in-tumor-microenvironment-is-associated-with-hepatocellular-carcinoma-differentiation-in-patients-undergoing-liver-transplantation/. Accessed June 7, 2025.

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