*Purpose: Response to locoregional therapy (LRT) in hepatocellular carcinoma (HCC) impacts both progression-free survival (PFS) and bridge to transplant success. Yttrium-90 (Y90) is an effective radioembolization for solitary, unresectable HCC with improved overall survival but its impact on T cells has not been fully detailed in bridged to transplant candidates. With the emergence of combination of LRT and immunotherapy, studies that investigate the effect of radioembolization on peripheral immune cells are lacking. In this study, we investigated radioembolization-induced changes in peripheral T cell phenotypes on objective response rates (ORR).

*Methods: Treatment-naïve HCC patients receiving Y90 as their first line LDT as a bridge to liver transplantation were prospectively enrolled. Preprocedural, follow-up, and longitudinal peripheral blood samples were collected, and T cells were characterized for lineage and phenotype by flow cytometry. ORR rates were assessed following treatment.

*Results: Study cohort was 75% BCLC-A, 61% ECOG-0, and 84% Child-Pugh. Patients were majority male (81%) with a cirrhosis etiology of hepatitis C (64%). Objective response to first line Y90 was found in 57% of cohort and associated with PFS (P<0.001, HR 0.24, CI 0.09 - 0.57). Complete blood counts before and after Y90 were compared to determine if radioembolization induced cytopenia. Matched pairs analysis revealed a 2.5-fold reduction in absolute lymphocytes counts (ALC, P<0.001) post-Y90 without changes to granulocytes or monocytes. Treatment-induced lymphopenia (ALC < 1.2 10³/μL) developed in 50% of cohort with normal ALC prior to Y90. In patients with pre-treatment lymphopenia, Y90 further decreased ALC. Characterization of T cell phenotypes at baseline and following Y90 showed changes in several T cell populations that were independent of cirrhosis etiology. Radioembolization caused an overall decrease in effector CD4 T cells (P<0.001) that was more pronounced in non-objective responders [objective responders: 31% to 27%, P=0.013; non-objective responders: 32% to 22%, P=0.007]. Y90 induced a decrease in naïve CD8 T cells (2.8% to 2.2%, P=0.039). Further, senescent CD8 T cells dramatically increased from 9% to 31% of total T cells following Y90 (P<0.001) independent of cirrhosis etiology and ORR. Y90 did not impact expression of exhausted T cell markers PD-1 or CTLA4.

*Conclusions: Radioembolization induces lymphopenia and further exacerbates T cells counts in lymphopenic patients. Sustained response to Y90 may account for increased senescent T cells in periphery. However, treatment-induced loss of effector T cells could impact ORR and PFS.

« Back to 2022 American Transplant Congress