The histological growth patterns in liver metastases from colorectal cancer display differences in lymphoid, myeloid, and mesenchymal cells

• Published in: MedComm (2020) 2024-12, Vol.5 (12), p.e70000-n/a
• Main Authors: Garcia‐Vicién, Gemma, Ruiz, Núria, Micke, Patrick, Ruffinelli, José Carlos, Mils, Kristel, Bañuls, María, Molina, Natalia, Pardo, Miguel A., Lladó, Laura, Mezheyeuski, Artur, Molleví, David G.
• Format: Article
• Language: English
• Subjects: capsule; desmoplasia; Fibroblasts; hepatic metastases; histologic growth pattern; Medical prognosis; Metastasis; microenvironment; Original
• ISSN: 2688-2663; 2688-2663
• DOI: 10.1002/mco2.70000

Colorectal liver metastases grow following different histologic growth patterns (HGPs), classified as desmoplastic and nondesmoplastic (dHGP, non‐dHGP), being the latter associated with worst prognosis. This study aimed to investigate the tumor microenvironment (TME) between HGPs supporting different survival. Multiplexed immunohistochemical staining was performed with the Opal7 system in a 100‐patients cohort to evaluate the tumor–liver interface with three different cell panels: lymphoid, myeloid, and carcinoma‐associated fibroblasts. Differences between HGPs were assessed by Mann–Whitney U test with Pratt correction and Holm–Bonferroni multitest adjustment. Cytotoxic T‐cells were more abundant in tumoral areas of dHGP, while non‐dHGP had higher macrophages infiltration, Th2, CD163+, and Calprotectin+ cells as well as higher pSMAD2 expression. Regarding carcinoma‐associated fibroblasts, several subsets expressing COL1A1 were enriched in dHGP, while αSMAlow_single cells were present at higher densities in non‐dHGP. Interestingly, Calprotectin+ cells confer better prognoses in non‐dHGP, identifying a subgroup of good outcome patients that unexpectedly also show an enrichment in other myeloid cells. In summary, our results illustrate different TME landscapes with respect to HGPs. dHGP presents a higher degree of immunocompetence, higher amounts of Collagen 1 as well as lesser presence of myeloid cell populations, features that might be influencing on the better prognosis of encapsulated metastases. Tumor microenvironment landscapes found in each histologic growth pattern. Two different TME scenarios are depicted depending on the HGP, where most nonencapsulated metastases display a highly immunosuppressive microenvironment while the better outcome of encapsulated metastases might be associated by the presence of cytotoxic T‐cells over the tumor nests and the restraining capabilities of an extracellular matrix enriched in Collagen 1. The dual role of Calprotectin, which seems to have a value dependent on HGP, is noteworthy.