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Ecto-calreticulin expression in multiple myeloma correlates with a failed anti-tumoral immune response and bad
Alfonso Serrano Del Valle1, Manuel Beltrán-Visiedo1, Victoria de Poo-Rodríguez2,3
1Apoptosis, Immunity & Cancer Group, IIS Aragón, University of Zaragoza, 50009 Zaragoza, Spain.
Abstract:
Immunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis. In the present study, we sought to evaluate CRT levels in the plasma membrane of CD38+ bone marrow mononuclear cells (BMMCs) isolated from 71 patients with varying degrees of multiple myeloma (MM) disease and examine the possible relationship between basal CRT exposure and the bone marrow immune microenvironment, as well as its connection with different clinical markers. Data show that increased levels of cell surface-CRT were associated with more aggressive clinical features and with worse clinical prognosis in MM. High CRT expression in MM cells was associated with increased infiltration of NK cells, CD8+ T lymphocytes and dendritic cells (DC), indicative of an active anti-tumoral immune response, but also with a significantly higher presence of immunosuppressive Treg cells and increased expression of PD-L1 in myeloma cells.
Insights
Calreticulin (CRT) exposure on multiple myeloma cells correlates with a more aggressive disease and worse prognosis. High CRT indicates an active immune response but also increased immunosuppression.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Immunogenic cell death (ICD) involves Damage Associated Molecular Patterns (DAMPs) like calreticulin (CRT).
- Increased CRT expression often correlates with better immunosurveillance and prognosis in some cancers.
- The role of CRT in multiple myeloma (MM) and its immune microenvironment requires further investigation.
Purpose of the Study:
- To evaluate cell surface calreticulin (CRT) levels on CD38+ bone marrow mononuclear cells (BMMCs) in multiple myeloma (MM) patients.
- To examine the relationship between CRT exposure and the bone marrow immune microenvironment in MM.
- To investigate the association of CRT levels with clinical markers and prognosis in MM.
Main Methods:
- Isolation of CD38+ bone marrow mononuclear cells (BMMCs) from 71 MM patients.
- Quantification of cell surface-calreticulin (CRT) expression.
- Analysis of immune cell infiltration (NK cells, CD8+ T cells, dendritic cells, Treg cells) and PD-L1 expression.
Main Results:
- Elevated cell surface-CRT levels in MM were linked to more aggressive disease features and poorer clinical outcomes.
- High CRT expression correlated with increased infiltration of anti-tumor immune cells (NK, CD8+ T, DC).
- Conversely, high CRT also associated with increased immunosuppressive Treg cells and PD-L1 expression on myeloma cells.
Conclusions:
- Cell surface-CRT expression in multiple myeloma is a marker of both active anti-tumor immunity and immune evasion.
- CRT levels in MM serve as a prognostic indicator, reflecting a complex interplay within the tumor immune microenvironment.
- Targeting CRT or associated pathways may offer novel therapeutic strategies for MM.
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