Tumour-induced immunosuppression and autocrine growth: Use of inducible anti TGF-β antisense RNA transfectants in a mesothelioma model

Fitzpatrick,; Bielefeldt‐Ohmann, Helle; Himbeck, RP; Jarnicki, AG; Marzo, AL; Robinson, Bws

doi:10.1016/0169-5002(96)81581-9

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is no explicit term for natural death of tumor cells; rather, it is taken into account in the growth term. Although there is evidence that TGF-β can promote tumor growth (Fitzpatrick et al, 1996), this effect is not included in this study.…”

Section: Equations 321 Tumor Cellsmentioning

confidence: 99%

A mathematical model of tumor–immune interactions

Robertson-Tessi

El-Kareh

Goriely³

2012

Journal of Theoretical Biology

150

127

View full text Add to dashboard Cite

A mathematical model of the interactions between a growing tumor and the immune system is presented. The equations and parameters of the model are based on experimental and clinical results from published studies. The model includes the primary cell populations involved in effector T-cell mediated tumor killing: regulatory T cells, helper T cells, and dendritic cells. A key feature is the inclusion of multiple mechanisms of immunosuppression through the main cytokines and growth factors mediating the interactions between the cell populations. Decreased access of effector cells to the tumor interior with increasing tumor size is accounted for. The model is applied to tumors with different growth rates and antigenicities to gauge the relative importance of various immunosuppressive mechanisms. The most important factors leading to tumor escape are TGF-β-induced immunosuppression, conversion of helper T cells into regulatory T cells, and the limitation of immune cell access to the full tumor at large tumor sizes. The results suggest that for a given tumor growth rate, there is an optimal antigenicity maximizing the response of the immune system. Further increases in antigenicity result in increased immunosuppression, and therefore a decrease in tumor killing rate. This result may have implications for immunotherapies which modulate the effective antigenicity. Simulation of dendritic cell therapy with the model suggests that for some tumors, there is an optimal dose of transfused dendritic cells.

show abstract

Section: Equations 321 Tumor Cellsmentioning

confidence: 99%