Dataset Information

Nwabugwu2013 - A Tumor-Immune Mathematical Model of CD4+ T Helper Cell

ABSTRACT: Its a mathematical model presenting the interaction between a growing tumor and immune system. Model involves tumor cells, dendritic cell, helper Tcells, regulatory Tcells, effector cells and certain cytokines (e.g. TGFbeta, IL10, IL2 ) produced by these cells. It represent a dynamic regulation of tumor production/killing by different immune cells and cytokines. Model is derived from Tessi-Roberton 2012

SUBMITTER: Krishna Kumar Tiwari

PROVIDER: MODEL2007090001 | BioModels | 2020-07-09

REPOSITORIES: BioModels

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MODEL2007090001?filename=24110741_Nwabugwu.cps	Other
	MODEL2007090001?filename=24110741_Nwabugwu.xml	Xml

Items per page:

1 - 2 of 2

Publications

A tumor-immune mathematical model of CD4+ T helper cell dependent tumor regression by oncogene inactivation.

Nwabugwu Chinyere I CI Rakhra Kavya K Felsher Dean W DW Paik David S DS

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 20130101

Understanding the complex dynamics between the tumor cells and the host immune system will be key to improved therapeutic strategies against cancer. We propose an ODE-based mathematical model of both the tumor and immune system and how they respond to inactivation of the driving oncogene. Our model supports experimental results showing that cellular senescence of tumor cells is dependent on CD4+ T helper cells, leading to relapse of tumors in immunocompromised hosts. ...[more]

PMID: 24110741

Similar Datasets

Project description:Immune evasion is an important hallmark of cancer ensured by diverse strategies, including immunosuppression and downregulation of antigen presentation. Here, to restore immunogenicity of cancer cells, we employed the minimal gene regulatory network of highly immunogenic type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen presenting cells (APCs). We showed that enforced expression of PU.1, IRF8 and BATF3 (PIB) was sufficient to induce cDC1 phenotype in 33 cell lines derived from human and mouse hematological and solid tumors. PIB gradually modified the cancer cell transcriptional and epigenetic program imposing global antigen presentation and cDC1 gene signatures within 9 days. cDC1 reprogramming restored the expression of antigen presentation complexes as well as co-stimulatory molecules at the cell surface, leading to the presentation of endogenous antigens on MHC-I, and to CD8+ T cell mediated killing. Functionally, tumor- APCs acquired the ability to uptake and process exogenous proteins and dead cells, secreted inflammatory cytokines and cross-presented antigens to naïve CD8+ T cells. Importantly, tumor-APCs were efficiently generated at the single cell level from primary cancer cells of 7 solid tumors that presented antigens to memory and naïve T-cells, as well as to activated patient-specific intra-tumoral lymphocytes. Alongside antigen presentation, tumor-APCs harboring TP53, KRAS and PTEN mutations showed impaired tumorigenicity in vitro and in vivo. Finally, using in vivo mouse models of melanoma, we showed that intra-tumoral injection of tumor-APCs promoted lymphoid infiltration, delayed tumor growth and increased survival. The anti-tumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors enabling tumor eradication. Our approach combines cDC1’s antigen processing and presenting abilities with endogenous generation of tumor antigens and serves as a platform for the development of novel immunotherapies based on endowed antigen presentation in cancer cells.