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Assessing the frequency of CD163+ tumor-associated macrophages and CD3+ T lymphocytes between MGUS and plasma cell
Aaron Niblock1, Simon Rajendran2, Charles Laverty2
1Queen Mary University, London, United Kingdom; School of Medicine, Ulster University, Northern Ireland.
Abstract:
Plasma cell dyscrasias (PCDs) are a heterogeneous group of diseases, and the most common is monoclonal gammopathy of undetermined significance (MGUS). This premalignant PCD consistently precedes multiple myeloma (MM), with a 1% risk of progression per year. Evading and suppressing the host immune system is an important step in the progression of MGUS to MM. This pilot study was designed to assess whether MGUS and MM have a distinct microenvironment, characterized by a unique distribution of immune cells, including tumor-associated macrophages. Evaluation of bone marrow (BM) tumor microenvironment was performed using immunohistochemical quantification of T cells (CD3), macrophages (CD68), and a macrophage subtype (CD163). The findings were compared between MGUS and MM to determine whether differences existed. The results suggest that there is a significantly lower percentage of CD3-positive, CD68-positive and CD163-positive immune effector cells in BM trephine biopsy samples from patients with MGUS than in those from patients with untreated MM (p < 0.001). Interestingly, in a patient treated for MM, the percentages of CD3+ and CD68+ cells were the same as those in other patients with untreated MM; however, the percentage of CD163+ cells reduced and correlated with low plasma cell count. Future studies are required to investigate whether the percentage of CD163+ cells is correlated with disease burden in patients with MM. If this is the case, then the level of soluble CD163 in plasma could be a potential biomarker of disease burden in patients with nonsecretory myelomas, in whom measurements of levels of paraprotein and free light chains are inconclusive.
Insights
Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) show distinct immune cell microenvironments. MGUS bone marrow has fewer immune cells, suggesting immune evasion in disease progression.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Plasma cell dyscrasias (PCDs) are a diverse group of disorders, with monoclonal gammopathy of undetermined significance (MGUS) being the most common.
- MGUS is a premalignant condition that precedes multiple myeloma (MM), carrying a 1% annual progression risk.
- Immune system evasion and suppression are critical in the progression from MGUS to MM.
Purpose of the Study:
- To investigate if MGUS and MM exhibit distinct bone marrow microenvironments.
- To analyze the distribution of immune cells, including tumor-associated macrophages, in MGUS versus MM.
Main Methods:
- Pilot study evaluating bone marrow (BM) microenvironment in MGUS and MM patients.
- Immunohistochemical quantification of T cells (CD3), macrophages (CD68), and CD163+ cells.
- Comparison of immune cell percentages between MGUS and untreated MM patient groups.
Main Results:
- Significantly lower percentages of CD3+, CD68+, and CD163+ immune cells were observed in MGUS BM samples compared to untreated MM (p < 0.001).
- A treated MM patient showed similar CD3+ and CD68+ cell counts to untreated MM patients.
- The treated MM patient exhibited reduced CD163+ cell percentages, correlating with a lower plasma cell count.
Conclusions:
- MGUS and MM possess distinct bone marrow immune microenvironments, with MGUS showing reduced immune cell infiltration.
- CD163+ cell levels may correlate with disease burden in MM, potentially serving as a biomarker, especially in nonsecretory myeloma.
