Booster Vaccinations against Cancer Are Critical in Prophylactic but Detrimental in Therapeutic Settings
| Autor: | Matteo Bellone, Anna Mondino, Alessia Ricupito, Arianna Calcinotto, Renato Longhi, Rodrigo Hess Michelini, Matteo Grioni |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Time Factors Cell Survival Immunization Secondary Melanoma Experimental Priming (immunology) Mice Transgenic CD8-Positive T-Lymphocytes Cancer Vaccines Disease-Free Survival Interferon-gamma Mice Immune system Cell Line Tumor Neoplasms Animals Medicine business.industry Hematopoietic Stem Cell Transplantation Dendritic Cells Dendritic cell Flow Cytometry Vaccine efficacy Mice Inbred C57BL Vaccination CTL Oncology Immunology Cytokines Female business Immunologic Memory CD8 T-Lymphocytes Cytotoxic Tramp |
| Zdroj: | Cancer research (Chic. Ill.) 73 (2013): 3545–3554. doi:10.1158/0008-5472.CAN-12-2449 info:cnr-pdr/source/autori:Ricupito, Alessia; Grioni, Matteo; Calcinotto, Arianna; Michelini, Rodrigo Hess; Longhi, Renato; Mondino, Anna; Bellone, Matteo/titolo:Booster Vaccinations against Cancer Are Critical in Prophylactic but Detrimental in Therapeutic Settings/doi:10.1158%2F0008-5472.CAN-12-2449/rivista:Cancer research (Chic. Ill.)/anno:2013/pagina_da:3545/pagina_a:3554/intervallo_pagine:3545–3554/volume:73 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-12-2449 |
| Popis: | Although cancer vaccines are in the clinic, several issues remain to be addressed to increase vaccine efficacy. In particular, whether how and how frequently a patient should be boosted remains to be defined. Here, we have assessed the ability of dendritic cell (DC)-based vaccines to induce a long-lasting tumor-specific CTL response in either prophylactic or therapeutic settings by taking advantage of transplantable and spontaneous mouse tumor models. Implementing a 24-hour ex vivo intracellular cytokine production assay, we have found that priming with a DC-based vaccine induced a long-lasting CTL response in wild-type mice, and homologous boosting better sustained the pool of central memory T cells, which associated with potent protection against B16F1 melanoma challenge. Appropriate timing of booster vaccination was also critical, as a tight boosting schedule hindered persistence of IFN-γ–competent memory CD8+ T cells and mice survival in prophylactic settings. Conversely, prime/boost vaccination proved to be of no advantage or even detrimental in therapeutic settings in B16F1 and transgenic adenocarcinoma of the mouse prostate (TRAMP) models, respectively. Although DC priming was indeed needed for tumor shrinkage, restoration of immune competence, and prolonged survival of TRAMP mice, repeated boosting did not sustain the pool of central memory CTLs and was detrimental for mice overall survival. Thus, our results indicate that booster vaccinations impact antitumor immunity to different extents, depending on their prophylactic or therapeutic administration, and suggest evaluating the need for boosting in any given patient with cancer depending on the state of the disease. Cancer Res; 73(12); 3545–54. ©2013 AACR. |
| Databáze: | OpenAIRE |
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