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[This corrects the article DOI: 10.1186/s40425-016-0157-6.].
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We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy followed by the PD-1-inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8+ T cells in the blood expanded and the ratio of CD8+:Treg T cells increased. A CD8+ T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone. Immunohistochemical analysis confirmed the presence of CD8+ T cells and low PD-L1 expression in the brain metastases before immunotherapy initiation. This sequence of therapy may provide an option for melanoma patients with unresponsive brain metastases. Cancer Immunol Res; 5(2); 100-5. ©2017 AACR.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Evolução Clonal , Irradiação Craniana , Melanoma/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Evolução Clonal/genética , Terapia Combinada , Irradiação Craniana/métodos , Feminino , Humanos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Imageamento por Ressonância Magnética , Melanoma/genética , Melanoma/metabolismo , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Immune related adverse events (irAEs) are common side effects of checkpoint inhibitory (CPI) therapies targeting CTLA-4 and PD-1/PD-L1. Grover's disease is an uncommon dermatologic condition with unclear pathogenesis previously reported as an irAE with ipilimumab. CASE PRESENTATION: We report an additional case of ipilimumab-induced Grover's disease. Interestingly, this dermatologic side effect did not appear with use of anti-PD-1 therapy in our patient. Immune analysis was performed and suggests a possible role of Th2 cells in its patholgenesis. CONCLUSION: This case suggests that Grover's disease is an irAE induced by Ipilimumab. Our immune analysis suggests that Th2 cells may be pathogenic mediators which warrants further study.