BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1909090003?filename=Shariatpanahi2018.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1909090003?filename=Shariatpanahi2018.cpsprimaryOK200Johannes MeyerNon-curatedordinary differential equation modelL2V4Immuno-oncologyhttps://www.ebi.ac.uk/biomodels/MODEL190909000329337259falseBioModelsModelsSBMLShariatpanahi2018 Mathematical modeling of tumor induced immunosuppression by myeloid derived suppressor cells2018MODEL1909090003Shariatpanahi SPShariatpanahi SP, Shariatpanahi SP, Madjidzadeh K, Hassan M, Abedi-Valugerdi M29337259,
Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs.. null, 442.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; Breast Cancer Research Center, ACECR, Tehran, Iran. Electronic address: pshariatpanahi@ut.ac.ir.johannes.p.meyer@gmail.comEMBL-EBIMyeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs.Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.Shariatpanahi Seyed Peyman SP, Shariatpanahi Seyed Pooya SP, Madjidzadeh Keivan K, Hassan Moustapha M, Abedi-Valugerdi Manuchehr MImmunosuppressive Therapy, MDSC, immunosuppression, Suppressor Cells, Myeloid Derived Suppressor Cells, Suppressor Cell, Cells, Myeloid-Derived Suppressor Cell., Myeloid-Derived, immunosuppressive therapy, Myeloid-Derived Suppressor, MDSCs, Immunosuppression, Myeloid Derived Suppressor Cell, Anti-Rejection Therapy, Tumor, CellImmunosuppressive Therapy, malignant Growth, MDSC, single-organism developmental process, experimental, HSN1E, Myeloid, region or site annotation, Effects, L-arginine, neoplasia, cell type cancer, postnatal development, number, EA1, Myeloid Derived Suppressor Cell, growth and development, neoplasm metastasis, Tumor, MLR-3, Long Term, cancer metastasis, binding site, L-(+)-arginine, period, AIM, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, reduced, Suppressor Cells, subnumerary, symptoms, Low, tiny, Immune., Arg, early activation antigen CD69, neoplasm, Effect, present in fewer numbers in organism, malignant tumour, Normalities, treatment, average, study, tumor cell migration, Immune Processes, positional, Immune Responses, (S)-2-amino-5-guanidinopentanoic acid, me75, methods, Longterm, activation inducer molecule, experimental section, cell process disease, tumor disease, neoplasm (disease), (S)-2-Amino-5-guanidinovaleric acid, R, hypoplasia, metastasis, present in organism, 5-fluoropyrimidine-2, Long-Term, number of, decreased number, 3H)-dione, D17Mit170, T1, CA, drugs, leukocyte surface antigen Leu-23, Immune Response, Immune, decreased, medicine, malignant neoplasm, has or lacks parts of type, disease management, Myeloid-Derived Suppressor, 5-fluorouracil, C-type lectin domain family 2 member C, MDSCs, L-Arg, site, Long-Term Effect, tumor, Anti-Rejection Therapy, Immune Process, 5-Fluoropyrimidine-2, tumor metastasis, Long-Term Effects, Myeloid Cell, accumulated, L-Arginin, 5-FU, small, screening, 5-Fluorouracil, malignancy, findings, intermittent, cou, immunosuppression, Process, fluorouracil, malignant, 5-Fluoracil, DNMT, natural killer, Longterm Effect, arginine, neoplastic disease, extra or missing physical or functional parts, Normalcy, MCMT, Tl3, Tl2, Cell, results, mereological quality, development, BL-AC/P26, neoplastic growth, Lr, MT, 4-dione, Suppressor Cell, interrupted, malignant neoplasm (disease), Long Term Effects, Myeloid-Derived, organ system cancer, immunosuppressive therapy, Immunosuppression, 4(1H, region, L-Arginine, CXXC9, early T-cell activation antigen p60, ADCADN, primary cancer, positional polypeptide feature, Myeloid Derived Suppressor Cells, underdeveloped, growth pattern, Normality, non-developmental growth, INSDC_feature:misc_binding, (2S)-2-amino-5-guanidinopentanoic acid, postnatal growth, signs, disease of cellular proliferation, malignant tumor, Longterm Effects, Fluorouracil, experimental procedures, Health, large granular lymphocyte, binding_or_interaction_site, GP32/28, malignant neoplastic disease, fluorouracilum, Cells, Myeloid-Derived Suppressor Cell, cardinality, Response, Bra, null cell, NK cell, fluorouracilo, other neoplasm, growth, cancer, time, CD69, CLEC2CImmunosuppressive Therapy, MDSC, immunosuppression., large granular lymphocyte, Suppressor Cells, Myeloid Derived Suppressor Cells, Suppressor Cell, Cells, Myeloid-Derived Suppressor Cell, Myeloid-Derived, Myeloid-Derived Suppressor, immunosuppressive therapy, MDSCs, natural killer, Immunosuppression, null cell, Myeloid Derived Suppressor Cell, NK cell, Anti-Rejection Therapy, Tumor, CellImmunosuppressive Therapy, MDSC, immunosuppression, Suppressor Cells, Myeloid Derived Suppressor Cells, Suppressor Cell, Cells, Myeloid-Derived Suppressor Cell., Myeloid-Derived, immunosuppressive therapy, Myeloid-Derived Suppressor, MDSCs, Immunosuppression, Myeloid Derived Suppressor Cell, Anti-Rejection Therapy, Tumor, CellfalseShariatpanahi2018 - Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells
This is a ODE-based mathematical model featuring equations describing the dynamics of tumor cells, cytotoxic T cells, natural killer cells, and myeloid-derived suppressor cells (MDSCs) that together describe the tumor-induced immunosuppression caused by MDSCs.
2019-09-092019-09-092019-09-09MODEL190909000329337259C45315C129908