Dormant Tumor Cell Vaccination: A Mathematical Model of Immunological Dormancy in Triple-Negative Breast Cancer.

Details

Serval ID
serval:BIB_BDD03A29D317
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dormant Tumor Cell Vaccination: A Mathematical Model of Immunological Dormancy in Triple-Negative Breast Cancer.
Journal
Cancers
Author(s)
Mehdizadeh R., Shariatpanahi S.P., Goliaei B., Peyvandi S., Rüegg C.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
11/01/2021
Peer-reviewed
Oui
Volume
13
Number
2
Pages
245
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Triple-negative breast cancer (TNBC) is a molecular subtype of breast malignancy with a poor clinical prognosis. There is growing evidence that some chemotherapeutic agents induce an adaptive anti-tumor immune response. This reaction has been proposed to maintain the equilibrium phase of the immunoediting process and to control tumor growth by immunological cancer dormancy. We recently reported a model of immunological breast cancer dormancy based on the murine 4T1 TNBC model. Treatment of 4T1 cells in vitro with high-dose chemotherapy activated the type I interferon (type I IFN) signaling pathway, causing a switch from immunosuppressive to cytotoxic T lymphocyte-dependent immune response in vivo, resulting in sustained dormancy. Here, we developed a deterministic mathematical model based on the assumption that two cell subpopulations exist within the treated tumor: one population with high type I IFN signaling and immunogenicity and lower growth rate; the other population with low type I IFN signaling and immunogenicity and higher growth rate. The model reproduced cancer dormancy, elimination, and immune-escape in agreement with our previously reported experimental data. It predicted that the injection of dormant tumor cells with active type I IFN signaling results in complete growth control of the aggressive parental cancer cells injected at a later time point, but also of an already established aggressive tumor. Taken together, our results indicate that a dormant cell population can suppress the growth of an aggressive counterpart by eliciting a cytotoxic T lymphocyte-dependent immune response.
Keywords
T lymphocytes, breast cancer, cancer cell vaccine, chemotherapy, immune-induced cancer dormancy, mathematical model, tumor heterogeneity, type I IFN
Pubmed
Web of science
Open Access
Yes
Create date
15/02/2021 12:02
Last modification date
07/07/2021 6:37
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