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

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....

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Bibliographic Details
Published in:Cancers 2022-01, Vol.14 (3), p.689
Main Authors: 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
Format: Article
Language:English
Subjects:
CD20 antigen
CD4 antigen
CD8 antigen
Cell density
Colorectal carcinoma
Cytotoxicity
desmoplasia
growth pattern
Growth patterns
Immunology
Immunotherapy
Infiltration
Invasiveness
Liver
Liver cancer
liver metastases
lymphocyte
Lymphocytes
Metastases
Metastasis
multiplex
Pathology
Spatial distribution
Statistical analysis
Stroma
Tumor cells
Tumor microenvironment
Tumors
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Summary: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 ( HGP) and non-desmoplastic ( HGP) metastases. The spatial evaluation reported that HGP-metastases displayed higher infiltration by CD8 and CD20 cells in peripheral regions as well as CD4 and CD45RO cells in HGP-metastases. However, the reactive stroma regions at the invasive margin (IM) of 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 ( < 0.05). Remarkably, the IM of HGP-metastases was characterized by higher infiltration of CD8 cells in the epithelial compartment parameter assessed with the ratio CD8 /CD8 , 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 HGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in HGP-metastases.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14030689