A tumor-immune interaction model for hepatocellular carcinoma based on measured lymphocyte counts in patients undergoing radiotherapy.
Clinical trials
Immune checkpoint inhibitor
Lymphocyte depletion
Mathematical modeling
Radiation therapy
Journal
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
20
03
2020
revised:
06
07
2020
accepted:
08
07
2020
pubmed:
18
7
2020
medline:
15
4
2021
entrez:
18
7
2020
Statut:
ppublish
Résumé
The impact of radiation therapy on the immune system has recently gained attention particularly when delivered in combination with immunotherapy. However, it is unclear how different treatment fractionation regimens influence the interaction between the immune system and radiation. The goal of this work was to develop a mathematical model that quantifies both the immune stimulating as well as the immunosuppressive effects of radiotherapy and simulates the effects of different fractionation regimens based on patient data. The framework describes the temporal evolution of tumor cells, lymphocytes, and inactivated dying tumor cells releasing antigens during radiation therapy, specifically modeling how recruited lymphocytes inhibit tumor progression. The parameters of the model were partly taken from the literature and in part extracted from blood samples (circulating lymphocytes: CLs) collected from hepatocellular carcinoma patients undergoing radiotherapy and their outcomes. The dose volume histograms to circulating lymphocytes were calculated with a probability-based model. Based on the fitted parameters, the model enabled a study into the depletion and recovery of CLs in patients as a function of fractionation regimen. Our results quantify the ability of short fractionation regimens to lead to shorter periods of lymphocyte depletion and predict faster recovery after the end of treatment. The model shows that treatment breaks between fractions can prolong the period of lymphocyte depletion and should be avoided. This study introduces a mathematical model for tumor-immune interactions using clinically extracted radiotherapy patient data, which can be applied to design trials aimed at minimizing lymphocyte depleting effects in radiation therapy.
Identifiants
pubmed: 32679308
pii: S0167-8140(20)30418-7
doi: 10.1016/j.radonc.2020.07.025
pmc: PMC8258732
mid: NIHMS1715728
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
73-81Subventions
Organisme : NCI NIH HHS
ID : P01 CA021239
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248901
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA241918
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA248118
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
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