Centro de Imunologia Molecular, Havana, Cuba

How regulatory CD25+CD4+T cells impinge on tumor immunobiology? On the differential response of tumors to immunotherapies.

Aiming to get a better insight on the impact of regulatory CD25+CD4+ T cells in tumor-immunobiology, a simple mathematical model was previously formulated and studied {Leon, 2006 #30}. This model predicts the existence of two alternative modes of unbounded tumor growth, which differ on their coupling with the immune system, providing a plausible explanation to the observation that the development of some tumors expand regulatory T cells while others do not. Here we report the follow-up study of how these two tumor classes respond to different therapies, namely vaccination, immune suppression, surgery, and different combinations... We show 1) how the timing and the dose applied in each particular treatment, determine whether the tumor will be rejected, with or without concomitant autoimmunity, or whether it will continue progressing with slower or faster pace; 2) that both regulatory T cell dependent and independent tumors are equally sensitive to vaccination, although former are more sensitive to T cell depletion treatments and are unresponsive to partial surgery alone; 3) that surgery, suppression, and vaccination treatments, can synergistically improve their individual effects, when properly combined. Particularly, we predict rational combinations helping to overcome the limitation of these individual treatments on the late stage of tumor development.

Instituto Gulbenkian de Ciência (Theoretical Epidemiology)

A new chaotic attractor in a dengue multi-strain model with temporary cross-immunity

An epidemic multi-strain model with temporary cross-immunity shows chaos, even in a previously unexpected parameter region. Dengue fever models have previously shown deterministic chaos with strong enhanced infectivity on secondary infection, motivated by experimental findings of antibody-dependent enhancement (ADE). Including temporary cross-immunity in such models, which is common knowledge among field researchers in dengue, we find a new deterministically chaotic attractor in an unexpected parameter region of reduced infectivity on secondary infection ("inverse ADE" parameter region). This is realistic for dengue fever since on second infection people are more likely to be hospitalized, hence do not contribute to the force of infection as much as people with first infection. Our finding has wider implications beyond dengue in any multi-strain epidemiological systems with altered infectivity upon secondary infection, since we can relax the condition of rather high infectivity on secondary infection previously required for deterministic chaos. For dengue, the finding of wide ranges of chaotic attractors open new ways to analysis of existing data sets.