Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.
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 antibo...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-04-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3084832?pdf=render |
| _version_ | 1811225197241434112 |
|---|---|
| author | Amy E Gilbert Panagiotis Karagiannis Tihomir Dodev Alexander Koers Katie Lacy Debra H Josephs Pooja Takhar Jenny L C Geh Ciaran Healy Mark Harries Katharine M Acland Sarah M Rudman Rebecca L Beavil Philip J Blower Andrew J Beavil Hannah J Gould James Spicer Frank O Nestle Sophia N Karagiannis |
| author_facet | Amy E Gilbert Panagiotis Karagiannis Tihomir Dodev Alexander Koers Katie Lacy Debra H Josephs Pooja Takhar Jenny L C Geh Ciaran Healy Mark Harries Katharine M Acland Sarah M Rudman Rebecca L Beavil Philip J Blower Andrew J Beavil Hannah J Gould James Spicer Frank O Nestle Sophia N Karagiannis |
| author_sort | Amy E Gilbert |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:02:43Z |
| format | Article |
| id | doaj.art-78cd2d0c45b44313a534ee2dfce6fb91 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T09:02:43Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-78cd2d0c45b44313a534ee2dfce6fb912022-12-22T03:39:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1933010.1371/journal.pone.0019330Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.Amy E GilbertPanagiotis KaragiannisTihomir DodevAlexander KoersKatie LacyDebra H JosephsPooja TakharJenny L C GehCiaran HealyMark HarriesKatharine M AclandSarah M RudmanRebecca L BeavilPhilip J BlowerAndrew J BeavilHannah J GouldJames SpicerFrank O NestleSophia N KaragiannisMelanoma, 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.http://europepmc.org/articles/PMC3084832?pdf=render |
| spellingShingle | Amy E Gilbert Panagiotis Karagiannis Tihomir Dodev Alexander Koers Katie Lacy Debra H Josephs Pooja Takhar Jenny L C Geh Ciaran Healy Mark Harries Katharine M Acland Sarah M Rudman Rebecca L Beavil Philip J Blower Andrew J Beavil Hannah J Gould James Spicer Frank O Nestle Sophia N Karagiannis Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. PLoS ONE |
| title | Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. |
| title_full | Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. |
| title_fullStr | Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. |
| title_full_unstemmed | Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. |
| title_short | Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. |
| title_sort | monitoring the systemic human memory b cell compartment of melanoma patients for anti tumor igg antibodies |
| url | http://europepmc.org/articles/PMC3084832?pdf=render |
| work_keys_str_mv | AT amyegilbert monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT panagiotiskaragiannis monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT tihomirdodev monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT alexanderkoers monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT katielacy monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT debrahjosephs monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT poojatakhar monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT jennylcgeh monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT ciaranhealy monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT markharries monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT katharinemacland monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT sarahmrudman monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT rebeccalbeavil monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT philipjblower monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT andrewjbeavil monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT hannahjgould monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT jamesspicer monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT frankonestle monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies AT sophiankaragiannis monitoringthesystemichumanmemorybcellcompartmentofmelanomapatientsforantitumoriggantibodies |