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. 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 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 _dHGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in _ndHGP-metastases.