Histopathological and Immune Prognostic Factors in Colo-Rectal Liver Metastases

SIMPLE SUMMARY: Clinical management of colo-rectal liver metastasis would benefit from a refined stratification of patients in prognostic groups, in order to identify the best therapeutic option. Efforts are ongoing in the definition of parameters associated with clinical behaviors, which could help classifying patients in clinically relevant groups. Here we aimed at discussing the recent advances in this field, and we introduced current and new promising candidates, such as morphological tumor features and immune components, which have been showing significant association with survival. Some of these parameters are slowly reaching the clinic and further efforts are ongoing in the attempt to combine them in multiparametric scores. ABSTRACT: Prognostic studies are increasingly providing new tools to stratify colo-rectal liver metastasis patients into clinical subgroups, with remarkable implications in terms of clinical management and therapeutic choice. Here, the strengths and hurdles of current prognostic tools in colo-rectal liver metastasis are discussed. Alongside more classic histopathological parameters, which capture features related to the tumor component, such as tumor invasion, tumor growth pattern and regression score, we will discuss immune mediators, which are starting to be considered important features. Their objective quantification has shown significant results in prognostication studies, with most of the work focused on adaptive immune cells, namely T cells. As for macrophages, they are only starting to be appreciated and we will present recent advances in evaluation of macrophage morphological features. Deeper knowledge acquired by multiparametric analyses is rapidly uncovering the variety of immune players that should be assessed. The future projection is to implement deep-learning histopathological tools and to integrate histopathological and immune metrics in multiparametric scores, with the ultimate objective to achieve a deeper resolution of the tumor features and their relevance for colo-rectal liver metastasis.