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Tytuł pozycji:

Modeling of tumor response to macrophage and T lymphocyte interactions in the liver metastatic microenvironment.

Tytuł :
Modeling of tumor response to macrophage and T lymphocyte interactions in the liver metastatic microenvironment.
Autorzy :
Curtis LT; Department of Bioengineering, University of Louisville, Lutz Hall 419, Louisville, KY, 40292, USA.
Sebens S; Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel (CAU), Kiel, Germany.; University Medical Center Schleswig-Holstein (UK-SH), Campus Kiel, Kiel, Germany.
Frieboes HB; Department of Bioengineering, University of Louisville, Lutz Hall 419, Louisville, KY, 40292, USA. .; Center for Predictive Medicine, University of Louisville, Louisville, KY, USA. .; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA. .
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Źródło :
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2021 May; Vol. 70 (5), pp. 1475-1488. Date of Electronic Publication: 2020 Nov 12.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: Berlin : Springer Verlag
Original Publication: Berlin ; New York, NY : Springer International, c1982-
MeSH Terms :
Models, Immunological*
Immunotherapy/*methods
Liver Neoplasms/*immunology
Macrophages/*immunology
Th1 Cells/*immunology
Th2 Cells/*immunology
Cell Communication ; Cell Differentiation ; Cytokines/metabolism ; Cytotoxicity, Immunologic ; Humans ; Liver Neoplasms/therapy ; Lymphocyte Activation ; Neoplasm Metastasis ; Th1-Th2 Balance ; Tumor Microenvironment
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Grant Information :
R15CA203605 United States CA NCI NIH HHS
Contributed Indexing :
Keywords: Cancer immunotherapy; Cancer simulation; Liver metastasis; Mathematical modeling; T lymphocytes; Tumor-associated macrophages
Substance Nomenclature :
0 (Cytokines)
Entry Date(s) :
Date Created: 20201112 Date Completed: 20210504 Latest Revision: 20210504
Update Code :
20210506
DOI :
10.1007/s00262-020-02785-4
PMID :
33180183
Czasopismo naukowe
The dynamic interactions between macrophages and T-lymphocytes in the tumor microenvironment exert both antagonistic and synergistic functions affecting tumor growth. Extensive experimental effort has been expended to investigate immunotherapeutic strategies targeting macrophage polarization as well as T-cell activation with the goal to promote tumor cell killing and cancer elimination. However, these interactions remain poorly understood, and cancer immunotherapeutic strategies are often disappointing. The complex system encompassing innate and adaptive immune cell activity in response to tumor growth could benefit from a systems perspective built upon mathematical modeling. This study develops a modeling system to help evaluate the effects of macrophage and T-lymphocyte interactions on tumor growth. The system enables simulating the combined cytotoxic and tumor-promoting interactions of these two immune cell populations in a vascularized organ microenvironment, such as in liver metastases. A hypothetical immunotherapeutic strategy is simulated to increase the number of tumor-suppressive (M1-phenotype) vs. tumor-promoting (M2-phenotype) macrophages to gauge their effects on CD8 + T-cells and CD4 + T-helper cells, which in turn affect the macrophage functions. The results highlight the dynamic interactions between macrophages and T-lymphocytes in the tumor microenvironment and show that with the chosen set of parameter values, the overall cytotoxic effect from macrophages and T-lymphocytes obtained by driving the M1:M2 ratio higher could saturate and fail to achieve tumor regression. Further expansion of this modeling platform to include additional tumor-immune cell interactions, coupled with parameters representing particular tumor characteristics, could enable systematic evaluation of immunotherapeutic strategies tailored to patient-tumor specific conditions, including metastatic disease.
Erratum in: Cancer Immunol Immunother. 2021 Jan 5;:. (PMID: 33398392)

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