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Article

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

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Tumoral and Stromal Chemoresistance Group, Oncobell Program, Institut d’Investigacions Biomèdiques de Bellvitge (IDIBELL), Gran Via 197-203, L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain
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Department of Immunology, Genetics and Pathology, Uppsala University, S-75105 Uppsala, Sweden
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Department of Pathology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain
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Department of Medical Oncology, Institut Català d’Oncologia, L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain
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Department of Surgery, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain
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Program Against Cancer Therapeutic Resistance (ProCURE), Institut Català d’Oncologia, L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain
*
Authors to whom correspondence should be addressed.
Academic Editors: Alessandro Ottaiano, Michele Caraglia and Luisa Circelli
Cancers 2022, 14(3), 689; https://doi.org/10.3390/cancers14030689
Received: 23 December 2021 / Revised: 25 January 2022 / Accepted: 27 January 2022 / Published: 29 January 2022
(This article belongs to the Special Issue Colorectal Cancer Metastasis)
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 (dHGP) and non-desmoplastic (ndHGP) metastases. The spatial evaluation reported that dHGP-metastases displayed higher infiltration by CD8+ and CD20+ cells in peripheral regions as well as CD4+ and CD45RO+ cells in ndHGP-metastases. However, the reactive stroma regions at the invasive margin (IM) of ndHGP-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 dHGP-metastases was characterized by higher infiltration of CD8+ cells in the epithelial compartment parameter assessed with the ratio CD8epithelial/CD8stromal, 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 dHGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in ndHGP-metastases. View Full-Text
Keywords: liver metastases; lymphocyte; immunology; desmoplasia; growth pattern; multiplex liver metastases; lymphocyte; immunology; desmoplasia; growth pattern; multiplex
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MDPI and ACS Style

Garcia-Vicién, G.; Mezheyeuski, A.; Micke, P.; Ruiz, N.; Ruffinelli, J.C.; Mils, K.; Bañuls, M.; Molina, N.; Losa, F.; Lladó, L.; Molleví, D.G. Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern. Cancers 2022, 14, 689. https://doi.org/10.3390/cancers14030689

AMA Style

Garcia-Vicién G, Mezheyeuski A, Micke P, Ruiz N, Ruffinelli JC, Mils K, Bañuls M, Molina N, Losa F, Lladó L, Molleví DG. Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern. Cancers. 2022; 14(3):689. https://doi.org/10.3390/cancers14030689

Chicago/Turabian Style

Garcia-Vicién, Gemma, Artur Mezheyeuski, Patrick Micke, Núria Ruiz, José Carlos Ruffinelli, Kristel Mils, María Bañuls, Natàlia Molina, Ferran Losa, Laura Lladó, and David G. Molleví. 2022. "Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern" Cancers 14, no. 3: 689. https://doi.org/10.3390/cancers14030689

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