Abstract 3840: Can serum exosomal content predict response to immunotherapy in hepatocellular carcinoma

Abstract

Abstract While atezolizumab and bevacizumab combination has received FDA approval for the treatment of unresectable hepatocellular carcinoma (HCC), and recently durvalumab + tremelimumab also showed activity over sorafenib, there is no biomarker which can guild which patients can benefit from these regimens. The traditional PD-L1 positivity in the tumor by immunohistochemical staining which can predict possible response to immune checkpoint inhibitor in other solid tumors, such as melanoma and NSCLC, does not appear to apply to HCC. Thus, we attempt to explore whether exosomal content can be useful to predict response. HCC tumors exist in a complex microenvironment and serum exosomes can be generated from either tumor cells, macrophages, or other immune cells. Exosome act as new mediators for cell-cell communication transporting molecules such as lipids, proteins, and RNAs in vivo. Exosomal PD1 and PD-L1 have been implicated for possible biomarkers for immune checkpoint sensitivity. We isolated exosome from serum of unresectable HCC patients who underwent treatment with atezolizumab and bevacizumab. Blood sample was obtained prior to treatment, and then on cycle 3 and at the time of disease progression. Exosomes were isolated using the kit from System BioScience. Twenty patients were entered into the study. Five patients were not treated (received SBRT or other regional treatment), one was lost to follow up and one had atezolizumab only. In terms of antitumor response, eight patients had stable disease, three patients had partial response and two patients had progressive disease. Serum exosomal content data was available in 16 patients. Both PD1 and PDL1 are lowest in the three patients who had response followed by the group who had stable disease. In the two patients who had progressive disease, both exosomal PD-L1 and PD1 appeared to be the highest and did not change during treatment. Unlike in melanoma patients we have studied, other proteins in the antiapoptotic family such as Bcl-2 do not show any differences. While the number of patients are small and accrual is still ongoing, it appears that exosomal PD-L1/PD1 may have clinical value in predicting response to atezolizumab + bevacizumab therapy. Supported by Sylvester Comprehensive Cancer Center grant. Citation Format: Niramol Savaraj, Pablo Puente, Ying-Ying Li, Chunjing Wu, Jonathan D. Nguyen, Medhi Wangpaichitr, Peter J. Hosein, Lynn G. Feun. Can serum exosomal content predict response to immunotherapy in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3840.