Unveiling Extramedullary Myeloma Immune Microenvironment: A Systematic Review

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Tumor ecosystems theory highlights microenvironment's role in cancer progression and therapy resistance.
• Multiple myeloma (MM) involves continuous clonal evolution, leading to aggressive extramedullary disease (EMD).
• The immune microenvironment (IME) is crucial in MM development and progression.

Purpose of the Study:

• To review the immune microenvironment (IME) in extramedullary plasma cell myeloma.
• To compare immune cell composition between medullary and extramedullary myeloma.
• To understand the role of IME in MM clonal evolution and extramedullary spread.

Main Methods:

• Systematic review adhering to PRISMA guidelines.
• Searched seven scientific databases.
• Included six studies meeting predefined inclusion criteria.

Main Results:

• Extramedullary disease (EMD) sites exhibit profound genetic instability and heterogeneous IME.
• EMD shows greater genetic and microenvironment variability than medullary disease.
• An immunosuppressive IME with exhausted immune cells and M2 macrophages is common in EMD, contrasting with tumor-free areas.

Conclusions:

• The interplay between the microenvironment and myeloma cells is critical.
• Targeting the IME can lead to novel therapeutic strategies for multiple myeloma.
• Understanding IME differences is essential for improving prognosis in extramedullary myeloma.