B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma
We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumo...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2011-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558611800825 |
| _version_ | 1811314186380115968 |
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| author | Marianela Candolfi James F. Curtin Kader Yagiz Hikmat Assi Mia K. Wibowo Gabrielle E. Alzadeh David Foulad AKM G. Muhammad Sofia Salehi Naomi Keech Mariana Puntel Chunyan Liu Nicholas R. Sanderson Kurt M. Kroeger Robert Dunn Gislaine Martins Pedro R. Lowenstein Maria G. Castro |
| author_facet | Marianela Candolfi James F. Curtin Kader Yagiz Hikmat Assi Mia K. Wibowo Gabrielle E. Alzadeh David Foulad AKM G. Muhammad Sofia Salehi Naomi Keech Mariana Puntel Chunyan Liu Nicholas R. Sanderson Kurt M. Kroeger Robert Dunn Gislaine Martins Pedro R. Lowenstein Maria G. Castro |
| author_sort | Marianela Candolfi |
| collection | DOAJ |
| description | We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumor regression in rodent models of glioblastoma. We investigated the role of B cells during immune-mediated glioblastoma multiforme regression. Although treatment with Ad-TK+Ad-Flt3L induced tumor regression in 60% of wild-type (WT) mice, it completely failed in B-cell-deficient Igh6-/- mice. Tumor-specific T-cell precursors were detected in Ad-TK+Ad-Flt3L-treated WT mice but not in Igh6-/- mice. The treatment also failed in WT mice depleted of total B cells or marginal zone B cells. Because we could not detect circulating antibodies against tumor cells and the treatment was equally efficient in WT mice and in mice with B-cell-specific deletion of Prdm 1 (encoding Blimp-1), in which B cells are present but unable to fully differentiate into antibody-secreting plasma cells, tumor regression in this model is not dependent on B cells’ production of tumor antigen-specific immunoglobulins. Instead, B cells seem to play a role as antigen-presenting cells (APCs). Treatment with Ad-TK+Ad-Flt3L led to an increase in the number of B cells in the cervical lymph nodes, which stimulated the proliferation of syngeneic T cells and induced clonal expansion of antitumor T cells. Our data show that B cells act as APCs, playing a critical role in clonal expansion of tumor antigen-specific T cells and brain tumor regression. |
| first_indexed | 2024-04-13T11:07:36Z |
| format | Article |
| id | doaj.art-4527ff1271c44c6f9dfe80d357ebd9d0 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T11:07:36Z |
| publishDate | 2011-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-4527ff1271c44c6f9dfe80d357ebd9d02022-12-22T02:49:13ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022011-10-01131094796010.1593/neo.11024B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for GlioblastomaMarianela Candolfi0James F. Curtin1Kader Yagiz2Hikmat Assi3Mia K. Wibowo4Gabrielle E. Alzadeh5David Foulad6AKM G. Muhammad7Sofia Salehi8Naomi Keech9Mariana Puntel10Chunyan Liu11Nicholas R. Sanderson12Kurt M. Kroeger13Robert Dunn14Gislaine Martins15Pedro R. Lowenstein16Maria G. Castro17Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USADepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USADepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USABiogen Idec, Immunology/Allergy, San Diego, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAWe have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumor regression in rodent models of glioblastoma. We investigated the role of B cells during immune-mediated glioblastoma multiforme regression. Although treatment with Ad-TK+Ad-Flt3L induced tumor regression in 60% of wild-type (WT) mice, it completely failed in B-cell-deficient Igh6-/- mice. Tumor-specific T-cell precursors were detected in Ad-TK+Ad-Flt3L-treated WT mice but not in Igh6-/- mice. The treatment also failed in WT mice depleted of total B cells or marginal zone B cells. Because we could not detect circulating antibodies against tumor cells and the treatment was equally efficient in WT mice and in mice with B-cell-specific deletion of Prdm 1 (encoding Blimp-1), in which B cells are present but unable to fully differentiate into antibody-secreting plasma cells, tumor regression in this model is not dependent on B cells’ production of tumor antigen-specific immunoglobulins. Instead, B cells seem to play a role as antigen-presenting cells (APCs). Treatment with Ad-TK+Ad-Flt3L led to an increase in the number of B cells in the cervical lymph nodes, which stimulated the proliferation of syngeneic T cells and induced clonal expansion of antitumor T cells. Our data show that B cells act as APCs, playing a critical role in clonal expansion of tumor antigen-specific T cells and brain tumor regression.http://www.sciencedirect.com/science/article/pii/S1476558611800825 |
| spellingShingle | Marianela Candolfi James F. Curtin Kader Yagiz Hikmat Assi Mia K. Wibowo Gabrielle E. Alzadeh David Foulad AKM G. Muhammad Sofia Salehi Naomi Keech Mariana Puntel Chunyan Liu Nicholas R. Sanderson Kurt M. Kroeger Robert Dunn Gislaine Martins Pedro R. Lowenstein Maria G. Castro B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma Neoplasia: An International Journal for Oncology Research |
| title | B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma |
| title_full | B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma |
| title_fullStr | B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma |
| title_full_unstemmed | B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma |
| title_short | B Cells Are Critical to T-cell—Mediated Antitumor Immunity Induced by a Combined Immune-Stimulatory/Conditionally Cytotoxic Therapy for Glioblastoma |
| title_sort | b cells are critical to t cell mediated antitumor immunity induced by a combined immune stimulatory conditionally cytotoxic therapy for glioblastoma |
| url | http://www.sciencedirect.com/science/article/pii/S1476558611800825 |
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