Cancer du poumon / Réponse immunitaire locale - modulation tumeur dépendante

Abstract : Lung cancer is the most frequent type of cancer in the world. Smoking is clearly the major cause of this pathology. The proliferation of tumor cells induces an inflammatory stromal reaction comprising numerous tumor-infiltrating lymphocytes. In this study, four complementary approaches have been used to study the tumor-dependent modulation of the immune system : TCR Vb repertoire usage in flow cytometry, TCRg gene clonal rearrangements in denaturing gradient gel electrophoresis (DGGE/TTGE), tumor and healthy lung tissue infiltration as well as lymph nodes characteristics in immunohistology and cytokine production by RNA RT-PCR. The results obtained have demonstrated the oligoclonality of T-cells in the three types of tissues tested. A Vb13.1 clone and a gamma clone appeared to be specifics of epidermoid carcinoma. Similarly, two TCRg clones appeared to be restricted to adenocarcinoma. Moreover, the CD3/TCR complex was clearly down regulated in tumors compared to healthy tissue or lymph nodes. Similarly, HLA-DR, HLA-DQ and b2 microglobuline, strongly expressed on healthy pneumocytes were nearly absent from tumor cells. Several cytokines with antagonistic effects were detected within tumoral tissue, especially TGFb and IL-10, which favour tumor growth and TNFalpha and IFNg which potentialize the anti-tumoral immune response. In conclusion, the clones identified in healthy lung tissue could be specific of early pre-tumoral lesions induced by tobacco smoke, and some of the clones appear to be tumor-specific. However, the immune system has been defeated by several mechanisms, including a decrease of the expression of partners of the immunological synapse and the production of antagonistic cytokines.
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Sophie Derniame. Cancer du poumon / Réponse immunitaire locale - modulation tumeur dépendante. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN10097⟩. ⟨tel-01748176⟩

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