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- Title
The commonality in the regulation of the immune response to most tumors: the prevalence of immune class deviation as a tumor escape mechanism and its significance for vaccination and immunotherapy.
- Authors
Hamilton, Duane H.; Bretscher, Peter A.
- Abstract
Observations in people and animals lead us to suggest that immune class deviation is much underrated as a mechanism of failure by the immune system to contain cancers. We argue that tumor regression usually correlates with strong and predominant cytotoxic T lymphocyte (CTL), Thi responses, whereas progression often correlates with the generation of a substantial and detrimental Th2-component of the anti-tumor immune response. We discuss here the grounds for this belief and how the recognition of the general prevalence of this tumor evasion mechanism opens up new approaches to vaccination and immunotherapy of cancer. We also argue that the existence of simple and practical means of longitudinally following the Thl/Th2 phenotype of the anti-tumor response is critical if immunotherapy is to be tailored to optimize the effectiveness of the patient's immunity against their cancer. Basic understanding of immune processes, and observations in murine tumor systems and human cancer, have led us to develop such means. Our approach follows from the fact that the prevalence of different IgG isotypes in anti-tumor IgG antibody reflects the cytokines produced by tumor-specific CD4 T cells, i.e. reflects their Th1/Th2 phenotype. Thus the relative predominance of different IgG isotypes reflects the Thl/Th2 phenotype of the anti-tumor immune response. We argue that most therapeutic interventions, in the form of removing or killing dividing tumor cells, have the capacity for not only eliminating tumor cells, but beneficially modulating the immune response towards an effective, predominant Thi mode, but only when these interventions are carried out to an optimal degree. Such beneficial modulation is readily achievable only if treatment is tailored to the particular circumstances of the patient, by longitudinally assessing how such treatment affects the Thl/Th2 phenotype of the anti-tumor response; this is necessary to adjust the treatment to optimally modulate the response to a predominant Th1 mode. We discuss the prospects for realizing such tailored immunotherapy.
- Subjects
IMMUNE system; T cells; SPONTANEOUS cancer regression; IMMUNE response; CYTOKINES
- Publication
Cancer Therapy, 2008, Vol 6, Issue 2, p745
- ISSN
1543-9135
- Publication type
Article