Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies
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Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. / Gilbert, Amy E; Karagiannis, Panagiotis; Dodev, Tihomir; Koers, Alexander; Lacy, Katie; Josephs, Debra H; Takhar, Pooja; Geh, Jenny L C; Healy, Ciaran; Harries, Mark; Acland, Katharine M; Rudman, Sarah M; Beavil, Rebecca L; Blower, Philip J; Beavil, Andrew J; Gould, Hannah J; Spicer, James; Nestle, Frank O; Karagiannis, Sophia N.
In: PLOS ONE, Vol. 6, No. 4, 29.04.2011, p. e19330.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies
AU - Gilbert, Amy E
AU - Karagiannis, Panagiotis
AU - Dodev, Tihomir
AU - Koers, Alexander
AU - Lacy, Katie
AU - Josephs, Debra H
AU - Takhar, Pooja
AU - Geh, Jenny L C
AU - Healy, Ciaran
AU - Harries, Mark
AU - Acland, Katharine M
AU - Rudman, Sarah M
AU - Beavil, Rebecca L
AU - Blower, Philip J
AU - Beavil, Andrew J
AU - Gould, Hannah J
AU - Spicer, James
AU - Nestle, Frank O
AU - Karagiannis, Sophia N
PY - 2011/4/29
Y1 - 2011/4/29
N2 - 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.
AB - 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.
KW - Antibodies, Monoclonal/chemistry
KW - Antibodies, Neoplasm/chemistry
KW - B-Lymphocytes/immunology
KW - Case-Control Studies
KW - Cell Line
KW - Cell Line, Tumor
KW - Cohort Studies
KW - Disease Progression
KW - Enzyme-Linked Immunosorbent Assay/methods
KW - Fibroblasts/metabolism
KW - Humans
KW - Immune System
KW - Immunoglobulin G/blood
KW - Immunohistochemistry/methods
KW - Melanoma/blood
KW - Time Factors
U2 - 10.1371/journal.pone.0019330
DO - 10.1371/journal.pone.0019330
M3 - SCORING: Journal article
C2 - 21559411
VL - 6
SP - e19330
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 4
ER -