Dendritic cells and their potential therapeutic role in haematological malignancy.
The generation of an effective immune response is dependent on the efficient capture and presentation of antigen by antigen-presenting cells. The most potent antigen-presenting cells are dendritic cells (DC). These cells have the capability of activating naive helper and cytotoxic T cells. In recent years it has been demonstrated that in vivo responses to a number of solid tumours can be generated by DC pulsed with either purified tumour antigen or whole tumour cell lysate. In addition, a number of in vivo studies using DC have also been attempted in solid tumours, with some encouraging results. In haematological malignancies, there is now strong evidence that previous T cell anergy can be reversed and significant anti-tumour immune responses generated, in vitro, against the majority of leukaemias. As far as in vivo studies in haematological malignancies are concerned, although T cell responses have been demonstrated in the majority of cases and some dramatic early clinical responses reported, overall results appear disappointing. However, considering the fact that many of these studies were performed in patients with advanced disease and that such therapeutic strategies are still in their infancy, the overall results are actually quite encouraging. Although there is a real potential for DC immunotherapy in the future, it is important to be realistic about the limitations and obstacles to its development. It is highly unlikely that any form of immunotherapy is going to be effective in advanced disease due to the physical bulk of tumour, the immunosuppressive effects of tumours themselves and to any secondary immunosuppression following standard cancer therapy. The potential for immunotherapy is likely to lie either in adjunctive therapy or for treating minimal residual disease. Even in those situations, one of the major obstacles to be overcome is the state of immunological anergy or tolerance that many tumours seem able to induce. Indeed, there is evidence that, under certain circumstances, DC themselves can present antigen in such a way as to produce this state of anergy. Although, in vitro manipulation of DC and T cells can generate tumour-specific T cells from previously "anergic" cells, once reintroduced in vivo, these cells will be re-exposed to the tumour environment with the risk of being rendered anergic again.
Kaminski
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ER
Plymouth Post-graduate Medical School, Derriford Combined Laboratories, Derriford Hospital, Plymouth PL6 8DH, UK. edward.kaminski@phnt.swest.nhs.uk
Goddard
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RV
Prentice
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AG
D019496:Cancer Vaccines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000502:physiology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*
D019496:Cancer Vaccines