Abstract 3171: Biomarkers of responses to immunotherapy in advanced hepatocellular carcinoma

Abstract

Abstract Biomarkers from the peripheral blood may serve as a useful tool to identify who will likely benefit from immunotherapy in patients with advanced hepatocellular carcinoma; hence, oncologists might be able to monitor treatment responses regularly via blood tests in addition to routine radiological assessment. To investigate immune profiles of patients with advanced HCC after exposure to immunotherapy by analysing circulating T cells from peripheral blood, our study included stage IV HCC patients (n = 14) seen at the Department of Medical Oncology, Queen Mary Hospitals. Nine patients received PD-1/PD-L1 inhibitor immunotherapy at the discretion of their clinicians, and five treatment-naïve patients were included as a control group. A control group of healthy subjects was also included in the study. Samples from patients who received PD-1/PD-L1 inhibitor therapy were collected after the treatment response was confirmed by radiological assessment. T cell profiles and exhaustion markers were compared along with treatment response as determined by radiological assessment. A total of 14 HCC patients were enrolled in the study: 4 patients showed a partial response to PD-1/PD-L1 inhibitor treatment, 5 patients progressed during PD-1/PD-L1 inhibitor treatment, and 5 patients were not treated with PD-1/PD-L1 inhibitors. Five buffy coat samples from healthy subjects were included as controls. Decreases in the percentage of regulatory T cells (0.8% of T cells in responders, p<0.0001) and in the ratio of effector memory T cells to regulatory T cells (EMT/Treg) were noted in patients who responded to PD-1/PD-L1 inhibitor therapy compared to those who did not, and thus may serve as biomarkers for immunotherapy responses in HCC. Similarly, we observed decreases in Tim-3 (2.09%, p<0.0001) and OX-40 (6.12%, p<0.0001) expression between responders and non-responders, and thus expression levels of these factors could potentially serve as response predictors. An increase in the proportion of CD4 CD8 double-positive (DP) T cells in peripheral blood was observed in immunotherapy responders (16.63%) versus non-responders (4.03%, p<0.05). Biomarkers in circulating T cells allow the investigation of immune profiles after treatment with immunotherapy using non-invasive approach from peripheral blood. Coupled with conventional surveillance strategies, we have identified biomarkers may serve as predictors for HCC patients who will likely benefit from immunotherapy. Citation Format: Vox Z. Ting, Valerie Chew, Carmen C. Wong, Thomas C. Yau. Biomarkers of responses to immunotherapy in advanced hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3171.