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

## TL;DR

This study finds that metastatic colorectal cancer tumors have a different tumor microenvironment compared to primary tumors, with higher immune cell infiltration and implications for patient survival.

## Contribution

The study reveals distinct immune infiltration patterns in primary versus metastatic colorectal tumors and links PD-L1 expression in primary tumors to improved survival.

## Key findings

- Metastatic tumors show higher immune cell infiltration compared to primary tumors.
- PD-L1 expression in primary tumors is positively correlated with better survival outcomes.
- Differences in immune infiltration are most pronounced in the central tumor region.

## Abstract

The tumor microenvironment (TME) is increasingly recognized as a key factor influencing the progression and response to treatment of cancers; however, its role in the evolution of the disease remains insufficiently understood. The aim of this retrospective study was to evaluate differences in the TME between primary and metastatic colorectal cancer tumors and to assess their potential impacts on the clinical course of the disease. Immunohistochemical analyses were performed on tissue samples obtained from primary and metastatic lesions, and immune cell infiltration characteristics were compared between tumor sites and across different stages of disease progression. Metastatic tumors exhibited more pronounced immune cell infiltration than primary lesions, with relevant differences observed predominantly within the central tumor region. These findings indicate that primary and metastatic tumors display distinct microenvironmental profiles. Assessment of the tumor immune landscape may therefore provide clinically relevant information and should be considered when planning therapeutic strategies and post-treatment surveillance in patients with colorectal cancer.

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.