Session Time: 6:00pm-7:00pm
Presentation Time: 6:20pm-6:25pm
*Purpose: T cell receptor (TCR) sequencing in hepatocellular carcinoma (HCC) patients revealed a diverse TCR repertoire in hepatitis B-associated HCC-infiltrating T cells. In this study, we investigate changes in TCR diversity in both viremic and nonviremic hepatitis C-associated HCC (HCV-HCC) patients following liver-directed therapy (LDT) and links to bridge to transplant waitlist outcome.
*Methods: HCV-HCC patients receiving LDT as a bridge to liver transplantation were prospectively enrolled at a high-volume transplant center. Peripheral blood T cells were characterized by flow cytometry at baseline and treatment follow-up as well as longitudinally while on the waitlist. T cell DNA isolated at each time point was sequenced and analyzed using ImmunoSeq Analyzer (Adaptive Biotechnologies). Response to LDT was assessed by mRECIST.
*Results: The cohort (n=17) was stratified based on HCV status (viremic n=10 and nonviremic n=7). Only 3 TCR clonotypes were shared over the entire cohort. Viremic HCV was associated with a more diverse T cell repertoire prior to and following LDT (P=0.007 and P=0.032). LDT resulted in a treatment-dependent increase in TCR diversity (P=0.034) and unique TCR clonotypes at follow-up independent of response to LDT. TCR diversity was strongly correlated with T cell senescence (CD57) as well as the PD-1 checkpoint inhibitor pathway in both CD4 (P=0.009 and P=0.037) and CD8 T cells (P=0.016 and P=0.019), respectively. Low TCR diversity following LDT was also associated with waitlist tumor progression (P=0.015). In patients successfully bridged to liver transplantation, 2.3-10.4% of intratumoral T cell clonotypes found in explant tumors were also found in circulating T cells prior to LDT. The percentage of clonotype overlap between TILs and circulating T cells did not change following treatment.
*Conclusions: The TCR repertoire is diverse in HCV-HCC patients and shifted based on viremic HCV status and LDT. HCV-HCC patients with low TCR diversity following treatment are at greater risk of tumor progression which may be mediated by T cell senescence and checkpoint inhibitory pathways. Longitudinal TCR profiling may uncover unique HCC biology or treatment pathways linked to effective neoantigen responses and improved bridge to transplant outcomes.
To cite this abstract in AMA style:Nunez K, Sandow T, Cohen A, Thevenot P. T Cell Repertoire Diversity in HCV-Associated Hepatocellular Carcinoma Patients Waitlisted for Liver Transplantation and Receiving Liver-Directed Therapy [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/t-cell-repertoire-diversity-in-hcv-associated-hepatocellular-carcinoma-patients-waitlisted-for-liver-transplantation-and-receiving-liver-directed-therapy/. Accessed June 18, 2021.
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