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PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival
BACKGROUND: Hepatocellular carcinoma (HCC) patients undergo liver-directed therapy (LDT) to control tumor burden while awaiting liver transplantation with response impacting waitlist survival. In this study, we investigate the link between absolute lymphocyte count (ALC) and PD-1 expression with res...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122885/ https://www.ncbi.nlm.nih.gov/pubmed/34689234 http://dx.doi.org/10.1007/s00262-021-03087-z |
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author | Núñez, Kelley G. Sandow, Tyler Fort, Daniel Hibino, Mina Wright, Paige Cohen, Ari J. Thevenot, Paul T. |
author_facet | Núñez, Kelley G. Sandow, Tyler Fort, Daniel Hibino, Mina Wright, Paige Cohen, Ari J. Thevenot, Paul T. |
author_sort | Núñez, Kelley G. |
collection | PubMed |
description | BACKGROUND: Hepatocellular carcinoma (HCC) patients undergo liver-directed therapy (LDT) to control tumor burden while awaiting liver transplantation with response impacting waitlist survival. In this study, we investigate the link between absolute lymphocyte count (ALC) and PD-1 expression with response to LDT and bridge-to-transplant survival. METHODS: Treatment-naïve HCC patients (n = 86) undergoing LDT were enrolled at a single center from August 2016–March 2020. Response to LDT was determined using mRECIST. Blood samples were collected on the day of LDT and at follow-up. Cells were analyzed for phenotype by flow cytometry. Outcomes were liver transplantation or tumor progression. RESULTS: Incomplete response to initial LDT was associated with tumor progression precluding liver transplantation (OR: 7.6, 1.7 – 33.3, P < 0.001). Univariate analysis of baseline T cell phenotypes revealed ALC (OR: 0.44, 0.24–0.85, P = 0.009) as well as intermediate expression of PD-1 on CD4 (OR: 3.3, 1.03–10.3, P = 0.034) and CD8 T cells (OR: 3.0, 0.99–8.8 P = 0.043) associated with incomplete response to LDT. Elevations in PD-1 expression were associated with increased risk of bridge-to-transplant tumor progression (HR: 3.2, 1.2–9.4). In patients successfully bridged to liver transplantation, pre-treatment peripheral PD-1 profile was associated with advanced tumor staging (P < 0.005) with 2/4 of patients with elevations in PD-1 having T3-T4 TNM staging compared to 0 with low PD-1 expression. CONCLUSION: Low lymphocyte count or elevated expression of the PD-1 checkpoint inhibitor is associated with incomplete response to LDT and increased risk of bridge-to-transplant tumor progression. Patients with impaired T cell homeostasis may benefit from PD-1 immunotherapy to improve response to LDT and improve bridge-to-transplant outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-021-03087-z. |
format | Online Article Text |
id | pubmed-9122885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-91228852022-05-22 PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival Núñez, Kelley G. Sandow, Tyler Fort, Daniel Hibino, Mina Wright, Paige Cohen, Ari J. Thevenot, Paul T. Cancer Immunol Immunother Original Article BACKGROUND: Hepatocellular carcinoma (HCC) patients undergo liver-directed therapy (LDT) to control tumor burden while awaiting liver transplantation with response impacting waitlist survival. In this study, we investigate the link between absolute lymphocyte count (ALC) and PD-1 expression with response to LDT and bridge-to-transplant survival. METHODS: Treatment-naïve HCC patients (n = 86) undergoing LDT were enrolled at a single center from August 2016–March 2020. Response to LDT was determined using mRECIST. Blood samples were collected on the day of LDT and at follow-up. Cells were analyzed for phenotype by flow cytometry. Outcomes were liver transplantation or tumor progression. RESULTS: Incomplete response to initial LDT was associated with tumor progression precluding liver transplantation (OR: 7.6, 1.7 – 33.3, P < 0.001). Univariate analysis of baseline T cell phenotypes revealed ALC (OR: 0.44, 0.24–0.85, P = 0.009) as well as intermediate expression of PD-1 on CD4 (OR: 3.3, 1.03–10.3, P = 0.034) and CD8 T cells (OR: 3.0, 0.99–8.8 P = 0.043) associated with incomplete response to LDT. Elevations in PD-1 expression were associated with increased risk of bridge-to-transplant tumor progression (HR: 3.2, 1.2–9.4). In patients successfully bridged to liver transplantation, pre-treatment peripheral PD-1 profile was associated with advanced tumor staging (P < 0.005) with 2/4 of patients with elevations in PD-1 having T3-T4 TNM staging compared to 0 with low PD-1 expression. CONCLUSION: Low lymphocyte count or elevated expression of the PD-1 checkpoint inhibitor is associated with incomplete response to LDT and increased risk of bridge-to-transplant tumor progression. Patients with impaired T cell homeostasis may benefit from PD-1 immunotherapy to improve response to LDT and improve bridge-to-transplant outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-021-03087-z. Springer Berlin Heidelberg 2021-10-24 2022 /pmc/articles/PMC9122885/ /pubmed/34689234 http://dx.doi.org/10.1007/s00262-021-03087-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Núñez, Kelley G. Sandow, Tyler Fort, Daniel Hibino, Mina Wright, Paige Cohen, Ari J. Thevenot, Paul T. PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival |
title | PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival |
title_full | PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival |
title_fullStr | PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival |
title_full_unstemmed | PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival |
title_short | PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival |
title_sort | pd-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122885/ https://www.ncbi.nlm.nih.gov/pubmed/34689234 http://dx.doi.org/10.1007/s00262-021-03087-z |
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