title: Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.
abstract: 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.
authors.affiliation: Cutaneous Medicine and Immunotherapy Unit, Division of Genetics and Molecular Medicine, NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London School of Medicine, St. John's Institute of Dermatology, Guy's Hospital, King's College London, London, United Kingdom.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Gilbert
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Karagiannis
authors.forename: Tihomir
authors.initials: T
authors.lastname: Dodev
authors.forename: Alexander
authors.initials: A
authors.lastname: Koers
authors.forename: Katie
authors.initials: K
authors.lastname: Lacy
authors.forename: Debra H
authors.initials: DH
authors.lastname: Josephs
authors.forename: Pooja
authors.initials: P
authors.lastname: Takhar
authors.forename: Jenny L C
authors.initials: JL
authors.lastname: Geh
authors.forename: Ciaran
authors.initials: C
authors.lastname: Healy
authors.forename: Mark
authors.initials: M
authors.lastname: Harries
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Acland
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Rudman
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Beavil
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Blower
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Beavil
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Gould
authors.forename: James
authors.initials: J
authors.lastname: Spicer
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Karagiannis
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D000912:Antibodies, Neoplasm / Q000737:chemistry*; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002460:Cell Line; D045744:Cell Line, Tumor; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry*; D007150:Immunohistochemistry / Q000379:methods; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G