Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern

In the era of immunotherapy, the tumor microenvironment (TME) has attracted special interest. However, colorectal liver metastases (CRC-LM) present histological peculiarities that could affect the interaction of immune and tumor cells such as fibrotic encapsulation and dense intratumoral stroma. We...

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Autores: Garcia Vicién, Gemma, Mezheyeuski, Artur, Micke, Patrick, Ruiz, Núria, Ruffinelli, José Carlos, Mils, Kristel, Bañuls, María, Molina, Natàlia, Losa, Ferran, Lladó, Laura, Molleví, David G.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/183996
Acceso en línea:https://hdl.handle.net/2445/183996
Access Level:acceso abierto
Palabra clave:Càncer de fetge
Càncer colorectal
Liver cancer
Colorectal cancer
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spelling Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth PatternGarcia Vicién, GemmaMezheyeuski, ArturMicke, PatrickRuiz, NúriaRuffinelli, José CarlosMils, KristelBañuls, MaríaMolina, NatàliaLosa, FerranLladó, LauraMolleví, David G.Càncer de fetgeCàncer colorectalLiver cancerColorectal cancerIn the era of immunotherapy, the tumor microenvironment (TME) has attracted special interest. However, colorectal liver metastases (CRC-LM) present histological peculiarities that could affect the interaction of immune and tumor cells such as fibrotic encapsulation and dense intratumoral stroma. We explored the spatial distribution of lymphocytic infiltrates in CRC-LM in the context of the histologic growth patterns using multispectral digital pathology providing data on three different scenarios, tumor periphery, invasive margin, and central tumoral areas. Our results illustrate a similar poor cell density of CD8(+) cells between different metastases subtypes in intratumoral regions. However, in encapsulated metastases, cytotoxic cells reach the tumor cells while remaining retained in stromal areas in non-encapsulating metastases. Some aspects are still unresolved, such as understanding the reason why most lymphocytes are largely retained in the capsule. Colorectal cancer liver metastases (CRC-LM) present differential histologic growth patterns (HGP) that determine the interaction between immune and tumor cells. We explored the spatial distribution of lymphocytic infiltrates in CRC-LM in the context of the HGP using multispectral digital pathology. We did not find statistically significant differences of immune cell densities in the central regions of desmoplastic ((d)HGP) and non-desmoplastic ((nd)HGP) metastases. The spatial evaluation reported that (d)HGP-metastases displayed higher infiltration by CD8(+) and CD20(+) cells in peripheral regions as well as CD4(+) and CD45RO(+) cells in (nd)HGP-metastases. However, the reactive stroma regions at the invasive margin (IM) of (nd)HGP-metastases displayed higher density of CD4(+), CD20(+), and CD45RO(+) cells. The antitumor status of the TIL infiltrates measured as CD8/CD4 reported higher values in the IM of encapsulated metastases up to 400 mu m towards the tumor center (p < 0.05). Remarkably, the IM of (d)HGP-metastases was characterized by higher infiltration of CD8(+) cells in the epithelial compartment parameter assessed with the ratio CD8(epithelial)/CD8(stromal), suggesting anti-tumoral activity in the encapsulating lesions. Taking together, the amount of CD8(+) cells is comparable in the IM of both HGP metastases types. However, in (d)HGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in (nd)HGP-metastases.MDPI AG2022202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/183996Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/cancers14030689Cancers, 2022, vol 14, num 3https://doi.org/10.3390/cancers14030689cc by (c) Garcia Vicién, Gemma et al, 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1839962026-05-29T05:05:01Z
dc.title.none.fl_str_mv Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
title Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
spellingShingle Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
Garcia Vicién, Gemma
Càncer de fetge
Càncer colorectal
Liver cancer
Colorectal cancer
title_short Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
title_full Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
title_fullStr Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
title_full_unstemmed Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
title_sort Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
dc.creator.none.fl_str_mv Garcia Vicién, Gemma
Mezheyeuski, Artur
Micke, Patrick
Ruiz, Núria
Ruffinelli, José Carlos
Mils, Kristel
Bañuls, María
Molina, Natàlia
Losa, Ferran
Lladó, Laura
Molleví, David G.
author Garcia Vicién, Gemma
author_facet Garcia Vicién, Gemma
Mezheyeuski, Artur
Micke, Patrick
Ruiz, Núria
Ruffinelli, José Carlos
Mils, Kristel
Bañuls, María
Molina, Natàlia
Losa, Ferran
Lladó, Laura
Molleví, David G.
author_role author
author2 Mezheyeuski, Artur
Micke, Patrick
Ruiz, Núria
Ruffinelli, José Carlos
Mils, Kristel
Bañuls, María
Molina, Natàlia
Losa, Ferran
Lladó, Laura
Molleví, David G.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de fetge
Càncer colorectal
Liver cancer
Colorectal cancer
topic Càncer de fetge
Càncer colorectal
Liver cancer
Colorectal cancer
description In the era of immunotherapy, the tumor microenvironment (TME) has attracted special interest. However, colorectal liver metastases (CRC-LM) present histological peculiarities that could affect the interaction of immune and tumor cells such as fibrotic encapsulation and dense intratumoral stroma. We explored the spatial distribution of lymphocytic infiltrates in CRC-LM in the context of the histologic growth patterns using multispectral digital pathology providing data on three different scenarios, tumor periphery, invasive margin, and central tumoral areas. Our results illustrate a similar poor cell density of CD8(+) cells between different metastases subtypes in intratumoral regions. However, in encapsulated metastases, cytotoxic cells reach the tumor cells while remaining retained in stromal areas in non-encapsulating metastases. Some aspects are still unresolved, such as understanding the reason why most lymphocytes are largely retained in the capsule. Colorectal cancer liver metastases (CRC-LM) present differential histologic growth patterns (HGP) that determine the interaction between immune and tumor cells. We explored the spatial distribution of lymphocytic infiltrates in CRC-LM in the context of the HGP using multispectral digital pathology. We did not find statistically significant differences of immune cell densities in the central regions of desmoplastic ((d)HGP) and non-desmoplastic ((nd)HGP) metastases. The spatial evaluation reported that (d)HGP-metastases displayed higher infiltration by CD8(+) and CD20(+) cells in peripheral regions as well as CD4(+) and CD45RO(+) cells in (nd)HGP-metastases. However, the reactive stroma regions at the invasive margin (IM) of (nd)HGP-metastases displayed higher density of CD4(+), CD20(+), and CD45RO(+) cells. The antitumor status of the TIL infiltrates measured as CD8/CD4 reported higher values in the IM of encapsulated metastases up to 400 mu m towards the tumor center (p < 0.05). Remarkably, the IM of (d)HGP-metastases was characterized by higher infiltration of CD8(+) cells in the epithelial compartment parameter assessed with the ratio CD8(epithelial)/CD8(stromal), suggesting anti-tumoral activity in the encapsulating lesions. Taking together, the amount of CD8(+) cells is comparable in the IM of both HGP metastases types. However, in (d)HGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in (nd)HGP-metastases.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/183996
url https://hdl.handle.net/2445/183996
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cancers14030689
Cancers, 2022, vol 14, num 3
https://doi.org/10.3390/cancers14030689
dc.rights.none.fl_str_mv cc by (c) Garcia Vicién, Gemma et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Garcia Vicién, Gemma et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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