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Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients

BACKGROUND: The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans. METHODS: I...

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Autores principales: Mignot, Grégoire, Hervieu, Alice, Vabres, Pierre, Dalac, Sophie, Jeudy, Geraldine, Bel, Blandine, Apetoh, Lionel, Ghiringhelli, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149472/
https://www.ncbi.nlm.nih.gov/pubmed/25170840
http://dx.doi.org/10.1371/journal.pone.0105907
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author Mignot, Grégoire
Hervieu, Alice
Vabres, Pierre
Dalac, Sophie
Jeudy, Geraldine
Bel, Blandine
Apetoh, Lionel
Ghiringhelli, François
author_facet Mignot, Grégoire
Hervieu, Alice
Vabres, Pierre
Dalac, Sophie
Jeudy, Geraldine
Bel, Blandine
Apetoh, Lionel
Ghiringhelli, François
author_sort Mignot, Grégoire
collection PubMed
description BACKGROUND: The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans. METHODS: In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests. RESULTS: We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4(+) T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control. CONCLUSION: Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers.
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spelling pubmed-41494722014-09-03 Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients Mignot, Grégoire Hervieu, Alice Vabres, Pierre Dalac, Sophie Jeudy, Geraldine Bel, Blandine Apetoh, Lionel Ghiringhelli, François PLoS One Research Article BACKGROUND: The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans. METHODS: In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests. RESULTS: We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4(+) T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control. CONCLUSION: Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers. Public Library of Science 2014-08-29 /pmc/articles/PMC4149472/ /pubmed/25170840 http://dx.doi.org/10.1371/journal.pone.0105907 Text en © 2014 Mignot et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mignot, Grégoire
Hervieu, Alice
Vabres, Pierre
Dalac, Sophie
Jeudy, Geraldine
Bel, Blandine
Apetoh, Lionel
Ghiringhelli, François
Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients
title Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients
title_full Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients
title_fullStr Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients
title_full_unstemmed Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients
title_short Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients
title_sort prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149472/
https://www.ncbi.nlm.nih.gov/pubmed/25170840
http://dx.doi.org/10.1371/journal.pone.0105907
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