IMMUNE FUNCTION OF DENDRITIC CELLS AGAINS T CANCERS

In tumor cells, abnormal proteins expression results from DNA mutation s or fusion associated with carcinogenesis or tumor progression. Those abnormal, often clearly defined proteins should be recognized by the immune system and induce an immune response leading to tumor rejection . Actually, most tumors escape the immune response through a specific tolerance, able to suppress or to modify the immune response against t umor associated antigens. Factors which contribute to tumor immunologi cal escape are not elucidated, but could involve a defect in tumor-ant igen presentation to the host immune system. An effective immune respo nse against tumor requires tumor-associated antigens to be processed i nto immunogenic peptides which are presented to T lymphocytes in assoc iation with MHC molecules. T-cell fonctional activation requires also a costimulatory signal delivered to the CD28 receptor on T cells by th e B7 family of molecules expressed by the antigen-presenting cells. Mo st tumor cells express MHC class I molecules, a minority also express MHC class II molecules and only a few lymphoma have been reported to e xpress B7. So, tumor cells are not able to present efficiently their s pecific antigens to competent T cells. Most tumors are yet infiltrated by inflammatory cells, some of them possessing the capacity to proces s tumor antigens and to present them to competent T cells, either insi de the tumor itself, or after migration into the draining lymph nodes. Among antigen-presenting cells, dendritic cells, unlike B lymphocytes and macrophages, are the only cells able to stimulate naive T lymphoc ytes. They present effectively antigens in situ and stimulate naive an d memory T lymphocytes into secondary lymphoid organs. Actually, dendr itic cells are supposed to take place in the antitumor immune response , and dendritic cells infiltration inside numerous neoplasms is often associated to an immune response against tumor. However, many question s still underline the failure to recognize stimuli involved in the mob ilization (and the retention ?) of dendritic cells inside tumor, or wh ich incite them to migrate out of it to ensure their antigen presentin g cell function effectively. The secretion of immunosuppressive factor s like IL-10, either by tumor cells and by tumor-infiltrating leukocyt es represents one of the mechanisms involved in the modulation of the antigen-presenting cell function and in tumor immunological escape. Re cent works were undertaken to increase tumor cells immunogenicity. B7. 1 molecule transfection allows tumor cells to present directly their a ntigens and leads to their eradication in vivo. Those results suggest that tumor-antigens presentation is limited in tumor-bearing hosts.