Abstract 1257: Ursolic acid modulates T Cell compartment of hepatocellular carcinoma
Authors: Lopez Patricia L. Da Costa , Cortes Andrea C. , Minamiguchi Kyiouki , Williams Malea L. , Dupuis Crystal J. , Anfossi Simone , Melancon Marites P. , Avritscher Rony 
Published: April 2023

Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with inflammation-associated. The cellular immune landscape of HCC can elucidate the tumor response and suggest the best strategy for effective T-cell responses. Ursolic acid (UA) is a pentacyclic triterpenoid with anti-inflammatory properties and can suppress tumor cells by oncogenic growth signaling and has known anti-inflammatory properties. To comprehend the effect of UA on the HCC immune landscape, we evaluated lymphoid cells in a syngeneic tumor model of an immunocompetent rat. The mcA-RH7777 rat cell line was implanted in Buffalo rats. The tumor size was verified with ultrasound, and rats received UA 75 mg/Kg or extra-virgin olive oil(EVOO), UA vehicle, by oral gavage every other day for 7 and 14 days. Tumor cells were isolated and stained with CD45, CD3, CD4, CD8, CD25, CD103, CD161, IL-17A, INFg, CD279/PD-1, FOXP3 antibodies. Immunophenotyping by spectral cytometry was analyzed in Flow Jo Software. The partial results from 7 and 14 days demonstrated UA had the same effect as EVOO. Tumor-infiltrated lymphocytes (TIL) were increased in EVOO and UA in 7 and 14 days of treatment in comparison with untreated tumors. For 7 days group, NK-like cells were higher in UA and EVOO than untreated (p=0.004 and p=0.004), while for 14 days there is a tendency to decrease it in oil and UA treatment. CD3+CD8+ (Tc) and CD3+CD4+(Th) populations seem reduced after oil and UA treatment. Also, both populations had low expression of INFg+ in all treatments and times used. EVOO may increase the population of CD25+FOXP3+(TREG) PD-1+ cells after 14 days of oil-only treatment. CD25+FOXP3+(TREG) INFg+ after very low representation in 7 days, seems to recover to normal level after 14 days in the UA group. UA group had tumors presenting more CD3+ (p=0.0004), CD3+CD4+ (Th), and CD3+/CD8+ (Tc) after 14 days (p=0.004 and p=0.0015 respectively). Evaluating the control rat liver (without tumor), we could see increased Th (p=0.02) and decreased Th17 cells (p=0.0002) in comparison with the liver surrounding the tumor untreated. The effect of UA was similar in the spleen. Tc (p=0.0015) and Th (p=0.0004) had a bigger population in the control and no activation of Tc and Th (INFg+) compared with the spleen of untreated tumor rats. UA in the liver and spleen, the decrease in the Th17, but not in the tumor. Maybe because tumors hadn't a consistent amount of Th17. EVOO seems to contribute to the infiltration of T cells, but not to activation of these cells. Oral gavage and olive oil may interpose the UA effect. The preliminary result using trans arterial embolization may be more effective as a combined strategy against HCC.
Citation Format: Patricia L. Da Costa Lopez, Andrea C. Cortes, Kyiouki Minamiguchi, Malea L. Williams, Crystal J. Dupuis, Simone Anfossi, Marites P. Melancon, Rony Avritscher. Ursolic acid modulates T Cell compartment of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1257.