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 ( d HGP) and non-desmoplastic ( nd HGP) metastases. The spatial evaluation reported that d HGP-metastases displayed higher infiltration by CD8 + and CD20 + cells in peripheral regions as well as CD4 + and CD45RO + cells in nd HGP-metastases. However, the reactive stroma regions at the invasive margin (IM) of nd 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 ( p < 0.05). Remarkably, the IM of d HGP-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 d HGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in nd HGP-metastases.