Les lymphomes T épidermotropes comme modèles de progression tumorale Epidermotropic T cell lymphomas as models for tumor progression

Résumé

Les lymphomes T cutanés sont liés à l’accumulation, dans la peau, de lymphocytes T matures mémoires à tropisme cutané. La forme la plus fréquente est le mycosis fongoïde, le syndrome de Sézary représentant la forme disséminée avec cellules tumorales circulantes. La physiopathologie et la progression tumorale restent mal comprises, mais plusieurs découvertes récentes suggèrent le développement possible de nouvelles possibilités thérapeutiques : mise en évidence de plusieurs antigènes exprimés par les lymphocytes T tumoraux, voies de signalisation impliquées dans la résistance à l’apoptose, possibilités de stimulation de l’immunité innée. La mise en évidence récente de signatures moléculaires devrait également permettre de mettre au point de nouveaux marqueurs diagnostiques et pronostiques.

Summary

Primary cutaneous T cell lymphomas (CTCL) represent the most frequently occurring group of extra-nodal T cell lymphomas, originating from skin-homing memory T cells. Sezary syndrome (SS) is a leukemic variant of CTCL that presents with erythroderma, lymphadenopathies and presence of malignant T cells in peripheral blood. SS has an unfavourable prognosis, and is refractory to current treatments. Progress in understanding the pathogenesis and tumor progression of SS is limited. In the past few years, we have identified and reported several CTCL-associated antigens, CD158k/KIR3DL2, CD85j/ILT2, and SC5/vimentin. KIR3DL2 is the first phenotypic marker of Sezary cells that can be used for the diagnostic and follow-up of Sezary syndrome. The SC5 antibody is the only monoclonal antibody reacting with vimentin on the surface of viable Sezary cells. CTCL are characterized by a predominance of Th2 cytokines. The recent suggestion that CTCL cells could be regulatory T (Tr) cells remains controversial. Gene expression studies suggest that in the future we may develop new diagnostic and prognostic tools, and identify subsets of patients who would benefit from more appropriate treatment protocols. Future challenges are to render tumor cells sensitive to apoptosis by inhibiting specific signalling pathways such as the constitutively activated NF-KB pathway, to identify specific surface kinase receptors and to develop specific inhibitors, to develop humanized monoclonal antibodies directed against tumor specific antigens, able to kill tumor cells via complement-dependent and antibody-dependent cytotoxicity, and to stimulate innate immunity.