Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma

Dendritic cells (DCs) are potent APCs and attractive vectors for cancer immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor that expresses low levels of MHC class I products, we investigated whether DCs loaded ex vivo with apoptotic tumor cells could elicit combined CD4+ a...

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Autores principales:	Goldszmid, Silvana Romina, Idoyaga, Juliana
Publicado:	2003
Materias:	CD4 antigen CD8 antigen gamma interferon major histocompatibility antigen class 1 tyrosinase related protein 2 animal cell animal experiment animal model antigen expression antigen recognition apoptosis article bone marrow cell cell culture cell maturation cell migration cell stimulation cellular immunity coculture controlled study cytokine release cytolysis dendritic cell experiment immunogenicity in vitro study in vivo study injection inoculation lymph node lymphatic drainage lymphocyte depletion male melanoma cell mouse nonhuman priority journal protein expression provocation test T lymphocyte target cell tumor cell tumor immunity vaccination
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n11_p5940_Goldszmid http://hdl.handle.net/20.500.12110/paper_00221767_v171_n11_p5940_Goldszmid
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00221767_v171_n11_p5940_Goldszmid
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spelling	paper:paper_00221767_v171_n11_p5940_Goldszmid2023-06-08T14:46:55Z Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma Goldszmid, Silvana Romina Idoyaga, Juliana CD4 antigen CD8 antigen gamma interferon major histocompatibility antigen class 1 tyrosinase related protein 2 animal cell animal experiment animal model antigen expression antigen recognition apoptosis article bone marrow cell cell culture cell maturation cell migration cell stimulation cellular immunity coculture controlled study cytokine release cytolysis dendritic cell experiment immunogenicity in vitro study in vivo study injection inoculation lymph node lymphatic drainage lymphocyte depletion male melanoma cell mouse nonhuman priority journal protein expression provocation test T lymphocyte target cell tumor cell tumor immunity vaccination Dendritic cells (DCs) are potent APCs and attractive vectors for cancer immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor that expresses low levels of MHC class I products, we investigated whether DCs loaded ex vivo with apoptotic tumor cells could elicit combined CD4+ and CD8+ T cell dependent, long term immunity following injection into mice. The bone marrow-derived DCs underwent maturation during overnight coculture with apoptotic melanoma cells. Following injection, DCs migrated to the draining lymph nodes comparably to control DCs at a level corresponding to ∼0.5% of the injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free 12 wk after challenge. CD4+ and CD8+ T cells were efficiently primed in vaccinated animals, as evidenced by IFN-γ secretion after in vitro stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma cells were recognized by immune CD8 + T cells in vitro, and cytolytic activity against tyrosinase-related protein 2180-188-pulsed target cells was observed in vivo. When either CD4+ or CD8+ T cells were depleted at the time of challenge, the protection was completely abrogated. Mice receiving a tumor challenge 10 wk after vaccination were also protected, consistent with the induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing apoptotic death can prime melanoma-specific helper and CTLs and provide long term protection against a poorly immunogenic tumor in mice. Fil:Goldszmid, R.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Idoyaga, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n11_p5940_Goldszmid http://hdl.handle.net/20.500.12110/paper_00221767_v171_n11_p5940_Goldszmid
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	CD4 antigen CD8 antigen gamma interferon major histocompatibility antigen class 1 tyrosinase related protein 2 animal cell animal experiment animal model antigen expression antigen recognition apoptosis article bone marrow cell cell culture cell maturation cell migration cell stimulation cellular immunity coculture controlled study cytokine release cytolysis dendritic cell experiment immunogenicity in vitro study in vivo study injection inoculation lymph node lymphatic drainage lymphocyte depletion male melanoma cell mouse nonhuman priority journal protein expression provocation test T lymphocyte target cell tumor cell tumor immunity vaccination
spellingShingle	CD4 antigen CD8 antigen gamma interferon major histocompatibility antigen class 1 tyrosinase related protein 2 animal cell animal experiment animal model antigen expression antigen recognition apoptosis article bone marrow cell cell culture cell maturation cell migration cell stimulation cellular immunity coculture controlled study cytokine release cytolysis dendritic cell experiment immunogenicity in vitro study in vivo study injection inoculation lymph node lymphatic drainage lymphocyte depletion male melanoma cell mouse nonhuman priority journal protein expression provocation test T lymphocyte target cell tumor cell tumor immunity vaccination Goldszmid, Silvana Romina Idoyaga, Juliana Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
topic_facet	CD4 antigen CD8 antigen gamma interferon major histocompatibility antigen class 1 tyrosinase related protein 2 animal cell animal experiment animal model antigen expression antigen recognition apoptosis article bone marrow cell cell culture cell maturation cell migration cell stimulation cellular immunity coculture controlled study cytokine release cytolysis dendritic cell experiment immunogenicity in vitro study in vivo study injection inoculation lymph node lymphatic drainage lymphocyte depletion male melanoma cell mouse nonhuman priority journal protein expression provocation test T lymphocyte target cell tumor cell tumor immunity vaccination
description	Dendritic cells (DCs) are potent APCs and attractive vectors for cancer immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor that expresses low levels of MHC class I products, we investigated whether DCs loaded ex vivo with apoptotic tumor cells could elicit combined CD4+ and CD8+ T cell dependent, long term immunity following injection into mice. The bone marrow-derived DCs underwent maturation during overnight coculture with apoptotic melanoma cells. Following injection, DCs migrated to the draining lymph nodes comparably to control DCs at a level corresponding to ∼0.5% of the injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free 12 wk after challenge. CD4+ and CD8+ T cells were efficiently primed in vaccinated animals, as evidenced by IFN-γ secretion after in vitro stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma cells were recognized by immune CD8 + T cells in vitro, and cytolytic activity against tyrosinase-related protein 2180-188-pulsed target cells was observed in vivo. When either CD4+ or CD8+ T cells were depleted at the time of challenge, the protection was completely abrogated. Mice receiving a tumor challenge 10 wk after vaccination were also protected, consistent with the induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing apoptotic death can prime melanoma-specific helper and CTLs and provide long term protection against a poorly immunogenic tumor in mice.
author	Goldszmid, Silvana Romina Idoyaga, Juliana
author_facet	Goldszmid, Silvana Romina Idoyaga, Juliana
author_sort	Goldszmid, Silvana Romina
title	Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
title_short	Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
title_full	Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
title_fullStr	Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
title_full_unstemmed	Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma
title_sort	dendritic cells charged with apoptotic tumor cells induce long-lived protective cd4+ and cd8+ t cell immunity against b16 melanoma
publishDate	2003
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n11_p5940_Goldszmid http://hdl.handle.net/20.500.12110/paper_00221767_v171_n11_p5940_Goldszmid
work_keys_str_mv	AT goldszmidsilvanaromina dendriticcellschargedwithapoptotictumorcellsinducelonglivedprotectivecd4andcd8tcellimmunityagainstb16melanoma AT idoyagajuliana dendriticcellschargedwithapoptotictumorcellsinducelonglivedprotectivecd4andcd8tcellimmunityagainstb16melanoma
_version_	1768544897478950912

Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma

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