[Frontiers in Bioscience S2, 1189-1197, June 1, 2010]

To suppress to rescue? Changing the approach for recalling anticancer immune responses

Luca Vannucci1, 2

1Laboratory of Natural Cell Immunity, Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic, and 2Laboratory of Tumor Biology, Department of Animal Embryology and Differentiation of Cells and Tissues, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, v.v.i., Libechov, Czech Republic


1. Abstract
2. Introduction
2. Introduction
3. Immune surveillance, tumor recognition, inflammation: some concepts
3.1. Immune surveillance and tumor cell phenotype
3.2. Inflammation and tumor inflammatory microenvironment
3.3. Three phases of tumor immune microenvironment development
4. The hypothesis: a non-unitary immunity and a normal homeostatic mechanism jam the anticancer immune response and need temporary immunosuppression to reset
4.1. Tumor escape as consequence of a homeostatic regulation
4.2. Treg cells, CD28, and "anticancer immunosuppressors"
5. Testing the hypothesis
6. Perspectives
7. Acknowledgements
8. References


The tumor microenvironment plays a fundamental role in both the organization of and the escape from anticancer immune response. Recent experimental approaches in anticancer therapy show that some anticancer chemotherapeutics - at a different dosage than usually used - can improve tumor control by acting on immunity and can also be used in immunosuppressive treatments. These apparently contrasting effects may provide an explanation by looking at the cancer immunity from a different perspective. Basing our hypothesis on the current inflammatory cancer microenvironment model, we suggest that the tumor escape may derive from a conflict between a deregulated local immune response and the application by the systemic immunity of a homeostatic regulation, physiologically used for terminating inflammatory processes. This regulation applied to the tumor microenvironment can contribute to impede the efficacy of anticancer responses. Therefore, we suggest recovering the anticancer response by paradoxically inducing a temporary immune suppression ("resetting" effect). In this paper, we review present concepts about inflammation and immunity in the cancer microenvironment, as well as experimental data from recent literature supporting this paradoxical intervention hypothesis.