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Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity

BACKGROUND: Perspectives of immunotherapy to cancer mediated by bone marrow transplantation (BMT) in conjunction with dendritic cell (DC)-mediated immune sensitisation have yielded modest success so far. In this study, we assessed the impact of DC on graft vs tumour (GvT) reactions triggered by allo...

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Autores principales: Gigi, V, Stein, J, Askenasy, N, Yaniv, I, Ash, S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619065/
https://www.ncbi.nlm.nih.gov/pubmed/23511628
http://dx.doi.org/10.1038/bjc.2013.39
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author Gigi, V
Stein, J
Askenasy, N
Yaniv, I
Ash, S
author_facet Gigi, V
Stein, J
Askenasy, N
Yaniv, I
Ash, S
author_sort Gigi, V
collection PubMed
description BACKGROUND: Perspectives of immunotherapy to cancer mediated by bone marrow transplantation (BMT) in conjunction with dendritic cell (DC)-mediated immune sensitisation have yielded modest success so far. In this study, we assessed the impact of DC on graft vs tumour (GvT) reactions triggered by allogeneic BMT. METHODS: H2K(a) mice implanted with congenic subcutaneous Neuro-2a neuroblastoma (NB, H2K(a)) tumours were irradiated and grafted with allogeneic H2K(b) bone marrow cells (BMC) followed by immunisation with tumour-inexperienced or tumour-pulsed DC. RESULTS: Immunisation with tumour-pulsed donor DC after allogeneic BMT suppressed tumour growth through induction of T cell-mediated NB cell lysis. Early post-transplant administration of DC was more effective than delayed immunisation, with similar efficacy of DC inoculated into the tumour and intravenously. In addition, tumour inexperienced DC were equally effective as tumour-pulsed DC in suppression of tumour growth. Immunisation of DC did not impact quantitative immune reconstitution, however, it enhanced T-cell maturation as evident from interferon-γ (IFN-γ) secretion, proliferation in response to mitogenic stimulation and tumour cell lysis in vitro. Dendritic cells potentiate GvT reactivity both through activation of T cells and specific sensitisation against tumour antigens. We found that during pulsing with tumour lysate DC also elaborate a factor that selectively inhibits lymphocyte proliferation, which is however abolished by humoral and DC-mediated lymphocyte activation. CONCLUSION: These data reveal complex involvement of antigen-presenting cells in GvT reactions, suggesting that the limited success in clinical application is not a result of limited efficacy but suboptimal implementation. Although DC can amplify soluble signals from NB lysates that inhibit lymphocyte proliferation, early administration of DC is a dominant factor in suppression of tumour growth.
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spelling pubmed-36190652014-03-19 Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity Gigi, V Stein, J Askenasy, N Yaniv, I Ash, S Br J Cancer Translational Therapeutics BACKGROUND: Perspectives of immunotherapy to cancer mediated by bone marrow transplantation (BMT) in conjunction with dendritic cell (DC)-mediated immune sensitisation have yielded modest success so far. In this study, we assessed the impact of DC on graft vs tumour (GvT) reactions triggered by allogeneic BMT. METHODS: H2K(a) mice implanted with congenic subcutaneous Neuro-2a neuroblastoma (NB, H2K(a)) tumours were irradiated and grafted with allogeneic H2K(b) bone marrow cells (BMC) followed by immunisation with tumour-inexperienced or tumour-pulsed DC. RESULTS: Immunisation with tumour-pulsed donor DC after allogeneic BMT suppressed tumour growth through induction of T cell-mediated NB cell lysis. Early post-transplant administration of DC was more effective than delayed immunisation, with similar efficacy of DC inoculated into the tumour and intravenously. In addition, tumour inexperienced DC were equally effective as tumour-pulsed DC in suppression of tumour growth. Immunisation of DC did not impact quantitative immune reconstitution, however, it enhanced T-cell maturation as evident from interferon-γ (IFN-γ) secretion, proliferation in response to mitogenic stimulation and tumour cell lysis in vitro. Dendritic cells potentiate GvT reactivity both through activation of T cells and specific sensitisation against tumour antigens. We found that during pulsing with tumour lysate DC also elaborate a factor that selectively inhibits lymphocyte proliferation, which is however abolished by humoral and DC-mediated lymphocyte activation. CONCLUSION: These data reveal complex involvement of antigen-presenting cells in GvT reactions, suggesting that the limited success in clinical application is not a result of limited efficacy but suboptimal implementation. Although DC can amplify soluble signals from NB lysates that inhibit lymphocyte proliferation, early administration of DC is a dominant factor in suppression of tumour growth. Nature Publishing Group 2013-03-19 2013-03-19 /pmc/articles/PMC3619065/ /pubmed/23511628 http://dx.doi.org/10.1038/bjc.2013.39 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Translational Therapeutics
Gigi, V
Stein, J
Askenasy, N
Yaniv, I
Ash, S
Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity
title Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity
title_full Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity
title_fullStr Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity
title_full_unstemmed Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity
title_short Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity
title_sort early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619065/
https://www.ncbi.nlm.nih.gov/pubmed/23511628
http://dx.doi.org/10.1038/bjc.2013.39
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