September 2, 2004
Melanoma: New Avenues For Therapy
A study by an Institut Pasteur team in association with Inserm, conducted in collaboration with the Dermatology Department of Saint-Louis Hospital and published in "The Journal of Immunology", has opened up significant hope for treating melanoma. The advance achieved by the researchers is especially noteworthy in the context of a serious cancer that often affects young subjects, and in which therapeutic progress has yet to be made.
Our immune system can naturally defend our body against some tumours, provided that it is not inhibited by certain mechanisms that put these tumours in a condition of "immunological escape". This problem has just been studied in the case of metastatic melanoma and has now resulted in the suggestion of new therapeutic strategies.
In the span of ten years, the incidence of melanoma has doubled. Currently there are about 8,000 new cases each year in France, and 50% of melanomas more than 1.5 mm thick will develop into a metastatic melanoma, which is practically incurable.
This research was conducted by Manuelle Viguier under the supervision of Laurent Ferradini in the Molecular Biology of the Gene Unit* (Institut Pasteur-Inserm Unit 277) -directed by Philippe Kourilsky- in collaboration with Hervé Bachelez (Dermatology Department and INSERM Unit 532 at Saint-Louis Hospital).
The researchers studied a series of patients suffering from metastatic melanomas affecting the lymph nodes. Extensive immunological studies were done on the patients’ metastatic lymph nodes, on tumor-free lymph nodes, and on the patients’ blood. These studies made it possible to demonstrate that some cells of the immune system, the Treg lymphocytes ("regulatory T lymphocytes"), acted as a major brake on the body’s natural defences against the tumour cells. In fact, at the metastatic lymph node level, several elements of the immune system (some T lymphocytes) are clearly present in order to launch an active defence against the tumour, but are greatly inhibited by the Treg cells.
The function of the Treg cells normally is to slow down immune responses and to prevent autoimmunity phenomena in the body -in other words to prevent the immune system from turning against one’s own cells. At the site of the tumour, they are also likely to prevent the immune defences from eliminating the tumour. This research has demonstrated that these cells are in fact present in twice the numbers in metastatic lymph nodes as in tumor-free lymph nodes or in the blood of melanoma patients.
The researchers thus concluded that an effective immunotherapy against metastatic melanoma should function by way of deleting Treg cells. Their hypothesis is backed up by earlier experiments conducted on animal tumour models that showed that the deletion of Treg cells (by blocking antibodies), in combination with immunotherapy, made it possible to heal these animals from their tumours permanently.
Following these results, the clinical objective for the researchers is now to organize a therapeutic trial in order to confirm this hypothesis in vivo.
This research was financed by the League Against Cancer (Paris Committee), the Association for Research Against Cancer, Inserm, and the Institut Pasteur.
* Now the Antiviral Immunity, Biotherapy and Vaccines Unit
Manuelle Viguier (1,2), Fabrice Lemaître (1), Olivier Verola (3), Min-Sun Cho (1), Guy Gorochov (4), Louis Dubertret (2), Hervé Bachelez (2), Philippe Kourilsky (1), et Laurent Ferradini (1)
1. Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur
2. Département de Dermatologie et INSERM U532, Institut de Recherche sur la Peau, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris
3. Département de Pathologie, Hôpital Saint-louis
4. Immunologie A, Centre d’Etude et de Recherche en Virologie et en Immunologie, Institut National de Science et de Recherche Médicale, Unité 543, Hôpital Pitié-Salpétrière
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