Evasion of tumours from the control of the immune system: consequences of brief encounters

Biology Direct

Mohannad Al-Tameemi²  Mark Chaplain²  Alberto d’Onofrio¹ 

[1] Department of Experimental Oncology, European Institute of Oncology, , Via Ripamonti 435, Milano, I-20141, Italy

[2] Division of Mathematics, University of Dundee, Dundee, Scotland, UK

关键词: Immuno-editing;    Diffusion;    Chemotaxis;    Mathematical models;    Immuno-evasion;    Cytotoxic T-lymphocytes;    Immune response;    Tumour growth;   

Others  :  1070626
DOI  :  10.1186/1745-6150-7-31

 received in 2012-02-06, accepted in 2012-07-26,  发布年份 2012

【 摘 要 】

Background

In this work a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. Specifically, attention is focused on the interactions between cytotoxic T-lymphocytes (CTLs) and tumour cells in a small, avascular multicellular tumour. At this stage of the disease the CTLs and the tumour cells are considered to be in a state of dynamic equilibrium or cancer dormancy. The precise biochemical and cellular mechanisms by which CTLs can control a cancer and keep it in a dormant state are still not completely understood from a biological and immunological point of view. The mathematical model focuses on the spatio-temporal dynamics of tumour cells, immune cells, chemokines and “chemorepellents” in an immunogenic tumour. The CTLs and tumour cells are assumed to migrate and interact with each other in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation of the lymphocytes and consequently the survival of the tumour cells. In the latter case, we assume that each tumour cell that survives its “brief encounter” with the CTLs undergoes certain beneficial phenotypic changes.

Results

We explore the dynamics of the model under these assumptions and show that the process of immuno-evasion can arise as a consequence of these encounters. We show that the proposed mechanism not only shape the dynamics of the total number of tumor cells and of CTLs, but also the dynamics of their spatial distribution. We also briefly discuss the evolutionary features of our model, by framing them in the recent quasi-Lamarckian theories.

Conclusions

Our findings might have some interesting implication of interest for clinical practice. Indeed, immuno-editing process can be seen as an “involuntary” antagonistic process acting against immunotherapies, which aim at maintaining a tumor in a dormant state, or at suppressing it.

Reviewers

This article was reviewed by G. Bocharov (nominated by V. Kuznetsov, member of the Editorial Board of Biology Direct), M. Kimmel and A. Marciniak-Czochra.

【 授权许可】

   
2012 Al-Tameemi et al.; licensee BioMed Central Ltd.

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