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

SIMPLE SUMMARY: 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 intratum...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833601/
https://www.ncbi.nlm.nih.gov/pubmed/35158957
http://dx.doi.org/10.3390/cancers14030689
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author 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_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_sort Garcia-Vicién, Gemma
collection PubMed
description SIMPLE SUMMARY: 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. ABSTRACT: 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 μm 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.
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spelling pubmed-88336012022-02-12 Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern 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. Cancers (Basel) Article SIMPLE SUMMARY: 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. ABSTRACT: 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 μm 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 2022-01-29 /pmc/articles/PMC8833601/ /pubmed/35158957 http://dx.doi.org/10.3390/cancers14030689 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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.
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833601/
https://www.ncbi.nlm.nih.gov/pubmed/35158957
http://dx.doi.org/10.3390/cancers14030689
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