Journal Article

Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies

Lacy, Katie, Geh, Jenny L. C., Beavil, Rebecca L., Blower, Philip J., Karagiannis, Panagiotis, Karagiannis, Sophia N., Nestle, Frank O., Beavil, Andrew J., Josephs, Debra H., Takhar, Pooja, Acland, Katharine M., Gilbert, Amy E., Koers, Alexander, Spicer, James, Healy, Ciaran, Harries, Mark, Gould, Hannah J., Dodev, Tihomir, Rudman, Sarah M.

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antibodies, Monoclonal - chemistry / Antibodies, Neoplasm - chemistry / B cells / B-Lymphocytes - immunology / Biology / Cancer / Cancer metastasis / Case-Control Studies / Cell Line / Cell Line, Tumor / Cohort Studies / Comparative analysis / Cytotoxicity / Development and progression / Disease Progression / Enzyme-linked immunosorbent assay / Enzyme-Linked Immunosorbent Assay - methods / Fibroblasts - metabolism / Humans / IgG antibody / Immune response (cell-mediated) / Immune response (humoral) / Immune System / Immunogenicity / Immunoglobulin G / Immunoglobulin G - blood / Immunoglobulin G - chemistry / Immunohistochemistry - methods / Immunological memory / Immunotherapy / Lymphocytes B / Lymphocytes T / Medicine / Melanoma / Melanoma - blood / Melanoma - immunology / Melanoma - therapy / Metastases / Monoclonal antibodies / Ovarian cancer / Patients / Peripheral blood / Skin / Skin cancer / Skin diseases / T cell receptors / T cells / Time Factors / Toxicity