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Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. T...

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Autores principales: Moshe, Adi, Izraely, Sivan, Sagi-Assif, Orit, Malka, Sapir, Ben-Menachem, Shlomit, Meshel, Tsipi, Pasmanik-Chor, Metsada, Hoon, Dave S.B., Witz, Isaac P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407964/
https://www.ncbi.nlm.nih.gov/pubmed/32668704
http://dx.doi.org/10.3390/cells9071683
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author Moshe, Adi
Izraely, Sivan
Sagi-Assif, Orit
Malka, Sapir
Ben-Menachem, Shlomit
Meshel, Tsipi
Pasmanik-Chor, Metsada
Hoon, Dave S.B.
Witz, Isaac P.
author_facet Moshe, Adi
Izraely, Sivan
Sagi-Assif, Orit
Malka, Sapir
Ben-Menachem, Shlomit
Meshel, Tsipi
Pasmanik-Chor, Metsada
Hoon, Dave S.B.
Witz, Isaac P.
author_sort Moshe, Adi
collection PubMed
description Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. Whereas cells of one melanoma acquired pro metastatic features following exposure to GM-CSF, cells from another melanoma either did not respond or became less malignant. We propose that inter-melanoma heterogeneity as manifested by differential responses of melanoma cells (and perhaps also of other tumor) to GM-CSF may be developed into a predictive marker providing a tool to segregate melanoma patients who will benefit from GM-CSF therapy from those who will not.
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spelling pubmed-74079642020-08-12 Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation Moshe, Adi Izraely, Sivan Sagi-Assif, Orit Malka, Sapir Ben-Menachem, Shlomit Meshel, Tsipi Pasmanik-Chor, Metsada Hoon, Dave S.B. Witz, Isaac P. Cells Article Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. Whereas cells of one melanoma acquired pro metastatic features following exposure to GM-CSF, cells from another melanoma either did not respond or became less malignant. We propose that inter-melanoma heterogeneity as manifested by differential responses of melanoma cells (and perhaps also of other tumor) to GM-CSF may be developed into a predictive marker providing a tool to segregate melanoma patients who will benefit from GM-CSF therapy from those who will not. MDPI 2020-07-13 /pmc/articles/PMC7407964/ /pubmed/32668704 http://dx.doi.org/10.3390/cells9071683 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Moshe, Adi
Izraely, Sivan
Sagi-Assif, Orit
Malka, Sapir
Ben-Menachem, Shlomit
Meshel, Tsipi
Pasmanik-Chor, Metsada
Hoon, Dave S.B.
Witz, Isaac P.
Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation
title Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation
title_full Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation
title_fullStr Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation
title_full_unstemmed Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation
title_short Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation
title_sort inter-tumor heterogeneity—melanomas respond differently to gm-csf-mediated activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407964/
https://www.ncbi.nlm.nih.gov/pubmed/32668704
http://dx.doi.org/10.3390/cells9071683
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