Abstract
Treatment of metastatic colorectal cancer is based upon the assumption that metastases are homogeneous within a patient. A comprehensive analysis of all metastases of each patient revealed the heterogeneity of the colorectal metastatic disease and its clinical impact. Complex tumor-immune interrelations shape the metastatic landscape. Adaptive immune cells and Immunoscore quantified in a random metastatic biopsy predict clinical outcome and their evaluation in the tumor microenvironment of the least infiltrated metastasis most accurately predict long-term survival. The adaptive immune cell infiltration was more informative than tumor regression and pathological response to predict long-term survival. These results highlight the clinical utility of Immunoscore for patient management. The immune response within the tumor microenvironment is an essential diagnostic criterion for colorectal cancer that has recently been integrated into the international WHO classification of Digestive System Tumors.