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Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma

Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density...

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Autores principales: Chakiryan, Nicholas H., Kimmel, Gregory J., Kim, Youngchul, Hajiran, Ali, Aydin, Ahmet M., Zemp, Logan, Katende, Esther, Nguyen, Jonathan, Lopez-Blanco, Neale, Chahoud, Jad, Spiess, Philippe E., Fournier, Michelle, Dhillon, Jasreman, Wang, Liang, Moran-Segura, Carlos, El-Kenawi, Asmaa, Mulé, James, Altrock, Philipp M., Manley, Brandon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059840/
https://www.ncbi.nlm.nih.gov/pubmed/33882057
http://dx.doi.org/10.1371/journal.pone.0245415
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author Chakiryan, Nicholas H.
Kimmel, Gregory J.
Kim, Youngchul
Hajiran, Ali
Aydin, Ahmet M.
Zemp, Logan
Katende, Esther
Nguyen, Jonathan
Lopez-Blanco, Neale
Chahoud, Jad
Spiess, Philippe E.
Fournier, Michelle
Dhillon, Jasreman
Wang, Liang
Moran-Segura, Carlos
El-Kenawi, Asmaa
Mulé, James
Altrock, Philipp M.
Manley, Brandon J.
author_facet Chakiryan, Nicholas H.
Kimmel, Gregory J.
Kim, Youngchul
Hajiran, Ali
Aydin, Ahmet M.
Zemp, Logan
Katende, Esther
Nguyen, Jonathan
Lopez-Blanco, Neale
Chahoud, Jad
Spiess, Philippe E.
Fournier, Michelle
Dhillon, Jasreman
Wang, Liang
Moran-Segura, Carlos
El-Kenawi, Asmaa
Mulé, James
Altrock, Philipp M.
Manley, Brandon J.
author_sort Chakiryan, Nicholas H.
collection PubMed
description Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we quantified cellular density and cellular clustering for myeloid cell markers in 129 regions of interest from 55 samples from 35 patients with metastatic ccRCC. CD68+ cells were found to be clustered with tumor cells and dispersed from stromal cells, while CD163+ and CD206+ cells were found to be clustered with stromal cells and dispersed from tumor cells. CD68+ density was not associated with OS, while high tumor/CD68+ cell clustering was associated with significantly worse OS. These novel findings would not have been identified if immune infiltrate was assessed using cellular density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors. Significance: Increased clustering of CD68+ TAMs and tumor cells was associated with worse overall survival for patients with metastatic ccRCC. This effect would not have been identified if immune infiltrate was assessed using cell density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors.
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spelling pubmed-80598402021-05-04 Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma Chakiryan, Nicholas H. Kimmel, Gregory J. Kim, Youngchul Hajiran, Ali Aydin, Ahmet M. Zemp, Logan Katende, Esther Nguyen, Jonathan Lopez-Blanco, Neale Chahoud, Jad Spiess, Philippe E. Fournier, Michelle Dhillon, Jasreman Wang, Liang Moran-Segura, Carlos El-Kenawi, Asmaa Mulé, James Altrock, Philipp M. Manley, Brandon J. PLoS One Research Article Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we quantified cellular density and cellular clustering for myeloid cell markers in 129 regions of interest from 55 samples from 35 patients with metastatic ccRCC. CD68+ cells were found to be clustered with tumor cells and dispersed from stromal cells, while CD163+ and CD206+ cells were found to be clustered with stromal cells and dispersed from tumor cells. CD68+ density was not associated with OS, while high tumor/CD68+ cell clustering was associated with significantly worse OS. These novel findings would not have been identified if immune infiltrate was assessed using cellular density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors. Significance: Increased clustering of CD68+ TAMs and tumor cells was associated with worse overall survival for patients with metastatic ccRCC. This effect would not have been identified if immune infiltrate was assessed using cell density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors. Public Library of Science 2021-04-21 /pmc/articles/PMC8059840/ /pubmed/33882057 http://dx.doi.org/10.1371/journal.pone.0245415 Text en © 2021 Chakiryan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chakiryan, Nicholas H.
Kimmel, Gregory J.
Kim, Youngchul
Hajiran, Ali
Aydin, Ahmet M.
Zemp, Logan
Katende, Esther
Nguyen, Jonathan
Lopez-Blanco, Neale
Chahoud, Jad
Spiess, Philippe E.
Fournier, Michelle
Dhillon, Jasreman
Wang, Liang
Moran-Segura, Carlos
El-Kenawi, Asmaa
Mulé, James
Altrock, Philipp M.
Manley, Brandon J.
Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
title Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
title_full Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
title_fullStr Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
title_full_unstemmed Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
title_short Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
title_sort spatial clustering of cd68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059840/
https://www.ncbi.nlm.nih.gov/pubmed/33882057
http://dx.doi.org/10.1371/journal.pone.0245415
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