Abstract 501P
Background
Colorectal liver metastases demonstrate distinct growth patterns reflecting differences in the interface between the metastatic tissue and surrounding liver parenchyma. Metastases of desmoplastic histopathological growth pattern (dHGP) are surrounded by a fibrotic capsule and patients with dHGP have improved prognosis in comparison to patients with non-desmoplastic growth pattern (non-dHGP). However, it remains unclear which mechanisms drive the contrast in survival outcome. Here we have investigated the differences in the immune infiltration in dHGP and non-dHGP metastases.
Methods
Multiplexed immunohistochemistry with markers for CD4, CD8a, FoxP3, CD20, CD45RO and pan-cytokeratin was performed on tissue samples from colorectal liver metastases (n= 12 and n=10 for dHGP and non-dHGP, respectively). Immune cell density distribution was evaluated at the periphery of metastases by measuring distances between the immune cells and the liver/metastasis interface.
Results
When analysing the distribution of the immune cells from liver/metastasis interface towards the centre of the metastasis (max depth 1500um), dHGP demonstrated 2 to 3-fold higher levels of CD8a+cell subsets (CD8a+ CD45RO- and CD8a+CD45RO+), CD4+CD45RO-, and similar levels of CD4+CD45RO+ cells in comparison to non-dHGP. Interestingly, even higher prevalence was seen in dHGP for Treg cells. Since this comparison included the immune cells in the peripheral fibrotic capsule (in dHGP), we next limited the analysis only to intratumoural areas. While having overall comparable levels for CD8a+cell subsets, non-dHGP tissue had significantly higher infiltration of CD4+subsets. Moreover, Tregs were only found in non-dHGP intratumoural tissue.
Conclusions
Spatial analysis of immune infiltration in the peripheral regions of liver metastases revealed complex patterns that differ between dHGP and non-dHGP. Thus, although dHGP is overall characterized by a more inflamed phenotype, the vast majority of immune infiltrate accumulated in the peripheral fibrotic capsule and don’t interact with cancer cells directly. Instead, intratumoural areas of non-dHGP had higher levels of CD4 cells and Tregs. This potentially reflects different mechanisms of interaction between malignant tissue, immune cells and fibrotic cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
P.O.Zetterling's foundation (Sweden); The Swedish Cancer Society; FI AGAUR; Proyecto FIS Ministerio de Sanidad.
Disclosure
All authors have declared no conflicts of interest.