Immune function of dendritic cells against cancers.

In tumor cells, abnormal proteins expression results from DNA mutations 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 tumor associated antigens. Factors which contribute to tumor immunological escape are not elucidated, but could involve a defect in tumor-antigen presentation to the host immune system. An effective immune response against tumor requires tumor-associated antigens to be processed into immunogenic peptides which are presented to T lymphocytes in association with MHC molecules. T-cell fonctional activation requires also a costimulatory signal delivered to the CD28 receptor on T cells by the B7 family of molecules expressed by the antigen-presenting cells. Most tumor cells express MHC class I molecules, a minority also express MHC class II molecules and only a few lymphoma have been reported to express B7. So, tumor cells are not able to present efficiently their specific antigens to competent T cells. Most tumors are yet infiltrated by inflammatory cells, some of them possessing the capacity to process tumor antigens and to present them to competent T cells, either inside 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 lymphocytes. They present effectively antigens in situ and stimulate naive and memory T lymphocytes into secondary lymphoid organs. Actually, dendritic 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 questions still underline the failure to recognize stimuli involved in the mobilization (and the retention ?) of dendritic cells inside tumor, or which incite them to migrate out of it to ensure their antigen presenting cell function effectively. The secretion of immunosuppressive factors like IL-10, either by tumor cells and by tumor-infiltrating leukocytes represents one of the mechanisms involved in the modulation of the antigen-presenting cell function and in tumor immunological escape. Recent works were undertaken to increase tumor cells immunogenicity. B7.1 molecule transfection allows tumor cells to present directly their antigens and leads to their eradication in vivo. Those results suggest that tumor-antigens presentation is limited in tumor-bearing hosts.