Objective:

To examine the specific mechanisms, such as tumor-secreted factors and immune cell interactions, underlying pre-metastatic niche formation in colorectal cancer (CRC) and how distinct immune landscapes in the liver and lung influence responses to immune checkpoint inhibitors (ICIs).

Key Findings:

• Liver metastases are associated with resistance to ICIs due to a highly tolerogenic and immunosuppressive microenvironment, necessitating alternative treatment strategies.
• Lung metastases show improved responses to ICIs, attributed to a more inflammatory and immune-reactive microenvironment, suggesting a need for tailored approaches.
• Differences in immune landscapes between organs significantly influence the efficacy of immunotherapy in metastatic CRC, highlighting the importance of organ-specific treatment considerations.

Interpretation:

The distinct immune environments of the liver and lung create variability in treatment responses to ICIs in metastatic CRC, necessitating organ-specific therapeutic strategies.

Limitations:

• Current evidence is limited and may not encompass all factors influencing PMN formation and ICI response, particularly regarding immune cell interactions and tumor microenvironment dynamics.
• Further research is needed to fully understand the biological mechanisms at play in different metastatic sites, including the role of specific cytokines and immune cell types.

Conclusion:

A deeper understanding of PMN biology and organ-specific immune regulation may enable more effective, tailored treatments for metastatic CRC.