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báo cáo hóa học:" Cytotoxic T lymphocyte responses against melanocytes and melanoma"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Cytotoxic T lymphocyte responses against melanocytes and melanoma | Chang et al. Journal of Translational Medicine 2011 9 122 http www.translational-medicine.eom content 9 1 122 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Cytotoxic T lymphocyte responses against melanocytes and melanoma Gwendolen Y Chang1 Holbrook E Kohrt1 Tor B Stuge1 Erich J Schwartz2 Jeffrey S Weber3 and Peter P Lee1 Abstract Background Vitiligo is a common toxicity associated with immunotherapy for melanoma. Cytotoxic T lymphocytes CTLs against melanoma commonly target melanoma-associated antigens MAAs which are also expressed by melanocytes. To uncouple vitiligo from melanoma destruction it is important to understand if CTLs can respond against melanoma and melanocytes at different levels. Methods To understand the dichotomous role of MAA-specific CTL we characterized the functional reactivities of established CTL clones directed to MAAs against melanoma and melanocyte cell lines. Results CTL clones generated from melanoma patients were capable of eliciting MHC-restricted MAA-specific lysis against melanocyte cell lines as well as melanoma cells. Among the tested HLA-A 0201-restricted CTL clones melanocytes evoked equal to slightly higher degranulation and cytolytic responses as compared to melanoma cells. Moreover MAA-specific T cells from vaccinated patients responded directly ex vivo to melanoma and melanocytes. Melanoma cells express slightly higher levels of MART-1 and gp100 than melanocytes as measured by quantitative reverse-transcriptase polymerase chain reaction qRT-PCR and immunohistochemistry. Conclusions Our data suggest that CTLs respond to melanoma and melanocytes equally in vitro and directly ex vivo. Introduction Recent FDA approval of ipilimumab for metastatic melanoma provides strong support for the ability of the immune system to mediate a beneficial effect against this disease. However immunotherapies for melanoma including ipilimumab 1 and adoptive cellular therapies 2 come with substantial toxicities including vitiligo 3-5 .