BACKGROUND: Melanoma is an immunogenic tumour. The development of skin depigmentation or melanoma-associated leucoderma (MAL) has been associated with favourable clinical outcome in patients with metastatic melanoma, especially after immunotherapy. Evidence for clinically meaningful enhancement of melanoma-directed autoimmunity, as indicated by MAL, after radiotherapy without immunotherapy has not yet been published. OBJECTIVES: We investigated whether a patient with stage IV melanoma, who developed leucoderma in the irradiated skin areas following radiotherapy and experienced exceptional disease-free survival of 3 years despite brain metastasis, possessed antimelanoma immunity that could be linked to the favourable disease course. METHODS: A detailed immunological analysis was performed consisting of immunohistochemistry of several melanoma tissues, and analyses of T cells isolated from the blood and MAL skin tissue for melanocyte/melanoma specificity and functionality, as well as the presence of a melanoma-specific antibody response. RESULTS: Immunological analyses showed the presence of CD8+ T cells and antibody responses directed against melanocyte differentiation antigens expressed in the primary tumour, lymph node and brain metastasis, indicating adequate tumour recognition by activated T cells. CONCLUSION: The immune responses found in this patient, probably enhanced by radiotherapy, are thought to have contributed to his favourable clinical course. Radiotherapy may act as local immunotherapy in patients with melanoma by destroying melanocytes, leading to the induction, or enhancement, of already existent antimelanoma immunity. As in patients treated with immunotherapy, this may lead to MAL, also at distant sites from the treated area. This patient is a clear example of the positive prognostic value of MAL, which is possibly induced by radiotherapy, for patients with melanoma.
BACKGROUND:Melanoma is an immunogenic tumour. The development of skin depigmentation or melanoma-associated leucoderma (MAL) has been associated with favourable clinical outcome in patients with metastatic melanoma, especially after immunotherapy. Evidence for clinically meaningful enhancement of melanoma-directed autoimmunity, as indicated by MAL, after radiotherapy without immunotherapy has not yet been published. OBJECTIVES: We investigated whether a patient with stage IV melanoma, who developed leucoderma in the irradiated skin areas following radiotherapy and experienced exceptional disease-free survival of 3 years despite brain metastasis, possessed antimelanoma immunity that could be linked to the favourable disease course. METHODS: A detailed immunological analysis was performed consisting of immunohistochemistry of several melanoma tissues, and analyses of T cells isolated from the blood and MAL skin tissue for melanocyte/melanoma specificity and functionality, as well as the presence of a melanoma-specific antibody response. RESULTS: Immunological analyses showed the presence of CD8+ T cells and antibody responses directed against melanocyte differentiation antigens expressed in the primary tumour, lymph node and brain metastasis, indicating adequate tumour recognition by activated T cells. CONCLUSION: The immune responses found in this patient, probably enhanced by radiotherapy, are thought to have contributed to his favourable clinical course. Radiotherapy may act as local immunotherapy in patients with melanoma by destroying melanocytes, leading to the induction, or enhancement, of already existent antimelanoma immunity. As in patients treated with immunotherapy, this may lead to MAL, also at distant sites from the treated area. This patient is a clear example of the positive prognostic value of MAL, which is possibly induced by radiotherapy, for patients with melanoma.
Authors: Ravi A Chandra; Tyler J Wilhite; Tracy A Balboni; Brian M Alexander; Alexander Spektor; Patrick A Ott; Andrea K Ng; F Stephen Hodi; Jonathan D Schoenfeld Journal: Oncoimmunology Date: 2015-05-28 Impact factor: 8.110
Authors: Clemens Grassberger; Susannah G Ellsworth; Moses Q Wilks; Florence K Keane; Jay S Loeffler Journal: Nat Rev Clin Oncol Date: 2019-06-26 Impact factor: 66.675
Authors: Hansje-Eva Teulings; Esther P M Tjin; Karina J Willemsen; Stephanie van der Kleij; Sylvia Ter Meulen; E Helen Kemp; Gabrielle Krebbers; Carel J M van Noesel; Cornelis L M C Franken; Jan W Drijfhout; Cornelis J M Melief; Ludmila Nieuweboer-Krobotova; Omgo E Nieweg; Jos A van der Hage; J P Wietze van der Veen; Germaine N Relyveld; Rosalie M Luiten Journal: Oncoimmunology Date: 2018-01-15 Impact factor: 8.110