期刊
PLOS ONE
卷 6, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0019330
关键词
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资金
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
- St. Thomas's NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust, UK
- CR UK/EPSRC/MRC/NIHR KCL/UCL Comprehensive Cancer Imaging Centre [C1519/A10331]
- Cancer Research UK [C30122/A11527]
- Mary Dunhill Trust
- CR UK/NIHR in England/DoH for Scotland
- Wales and Northern Ireland Experimental Cancer Medicine Centre (FON)
- Overseas Research Students Award Scheme (AEG)
- Medical Research Council [G1000758B, G0501494, G0600698B, G1000758] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10212] Funding Source: researchfish
- MRC [G0501494] Funding Source: UKRI
Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P < 0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P < 0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.
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