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TUMOURIMMUNOLOGY - PRESENT STATUS AND LESSONS FROM THE 1ST INTERNATIONAL CONFERENCE ON BASIC AND CLINICAL IMMUNOGENOMICS. PARTI-EVTERACTIONBETWEENTHE TUMOUR AND THE IMMUNESYSTEM  
HATINA J. 

UNIVERSITA KARLOVA, LÉKAŘSKÁ FAKULTA V PLZNI, ÚSTAV BIOLOGIE
 


Summary:

       Tumour development is generally accompanied by a spontaneous immune response towards the developing tumour. Tumour cells bear a lot of tumour antigens, which are specifically recognized by immune cells. Tumour antigens are either new protein sequences resulting from somatic mutagenesis, splicing errors etc. in oncogenes and tumour suppressor genes (tumour-specific antigens), or normál cellular proteins overexpressed or aberrantly expressed by the tumour. These latter tumour-associated antigens are either a remnant of genes expressed in a cell type, from which the tumour originates, or result from globál changes in the expression of genome along the tumour development and progression. Identification of tumour antigens has been traditionally based on immunological techniques, new tumour antigens are nowadays more frequently identified, however, by means of molecular biology and especially genomics. The relationship between the tumour and the immune systém is best characterized in terms of a complex mutual interaction, which takés different forms as the tumour is initiated and develops. Three stages are generally distinguished. Initially, the immune systém manages to control the tumourigenic process, either by eliminating initiated tumour cells (immune surveillance) or by keeping the tumour cell population at a constant, tiny number (equilibrium). Development of clinical cancer implies previous loss of this immune control (escape). Two groups of processes underlie the escape of tumour cells - tumour-induced immunosuppression and loss of immune recognition structures from escaping tumour cells. The tumour-induced immunosuppression can result from expression of specific signalling molecules on the surface of tumour cells (fasL), secretion of specific immunosuppressive cytokines (TGF- f$,1L-10), or from changes in differentiation of helper T-lymphocytes along the Thl/Th2 paradigm. Various other specialized leukocyte populations are involved in the complex interaction between the tumour and the immune systém, notably cytotoxic T-lymphocytes, which provide the main effector antitumour population, tumour associated macrophages and regulátory T-cells. Different tumour antigens tend to induce the immune response with markedly different efficacy, resulting in immunodominance of some antigens. Besides, the immune system might be regarded as an important selection pressure driving the development of tumour escape variants, a process termed immunoediting.

        Key words: tumour antigens, immune surveillance, escape from immune control, tumour-induced immunosuppression, regulátory T-cells, Thl/Th2 polarization
       

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