Disparities in Tumor Microenvironment Between Primary and Metastatic Colorectal Cancer: Impact on Immune Infiltration and Survival.

BACKGROUND/OBJECTIVES: In recent years, growing evidence that the tumor microenvironment (TME) plays crucial roles in the progression and treatment responses of various cancers has emerged. Unfortunately, we still do not fully understand the mechanisms through which the TME influences cancer development. Therefore, the aim of this study is to assess the impact of the TME on the clinical course of the disease, comparing primary and metastatic tumors. MATERIALS AND METHODS: This retrospective study included 30 colorectal cancer patients for which tissue samples from primary and metastatic tumors were available for immunohistochemistry. A multiple Cox proportional hazards regression analysis was performed to characterize differences between the microenvironments of primary and metastatic tumors, as well as between lesions diagnosed at different times after resection. RESULTS: Immune cell infiltration was higher in metastatic than primary tumors. Statistically significant differences were observed only in the central part of the tumor, while cell infiltration at the periphery had no prognostic significance. In the multivariate analysis, a positive correlation was revealed between the expression of Programmed Death-Ligand 1 (PD-L1) on primary tumor cells (TCs) and survival (HR: 5.43; 95% CI: 1.89-15.61; p = 0.0017). CONCLUSIONS: Primary and metastatic tumors differ regarding their tumor microenvironment. As such, the tumor immune status should be considered as a key factor when selecting a therapeutic strategy, as well as for post-treatment surveillance.