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

Abstract

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 thatd HGP-metastases displayed higher infiltration by CD8+ and CD20+ cells in peripheral regions as well as CD4+ and CD45RO+ cells innd HGP-metastases. However, the reactive stroma regions at the invasive margin (IM) ofnd 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 ofd HGP-metastases was characterized by higher infiltration of CD8+ cells in the epithelial compartment parameter assessed with the ratio CD8epithelial /CD8stromal, 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, ind HGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas innd HGP-metastases.