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Cytofluorometric assessment of calreticulin exposure on CD38 plasma cells from the human bone marrow. | LitMetric

AI Article Synopsis

  • Exposure of calreticulin (CALR) on the surface of stressed and dying cells is crucial for their effective uptake by antigen-presenting cells like dendritic cells, aiding in the adaptive immune response and memory formation.
  • In contrast, the presence of phosphatidylserine (PS) signals tolerogenic macrophages for quick engulfment of dying cells, highlighting different immune responses.
  • The article outlines a protocol for using flow cytometry to measure CALR and PS on plasma cells in multiple myeloma patients, and suggests this method can be adapted for use with other cancers as well.

Article Abstract

Exposure of the endoplasmic reticulum chaperone calreticulin (CALR) on the surface of stressed and dying cells is paramount for their effective engulfment by professional antigen-presenting cells such as dendritic cells (DCs). Importantly, this is required (but not sufficient) for DCs to initiate an adaptive immune response that culminates with an effector phase as well as with the establishment of immunological memory. Conversely, the early exposure of phosphatidylserine (PS) on the outer layer of the plasma membrane is generally associated with the rapid engulfment of stressed and dying cells by tolerogenic macrophages. Supporting the clinical relevance of the CALR exposure pathway, the spontaneous or therapy-driven translocation of CALR to the surface of malignant cells, as well as intracellular biomarkers thereof, have been associated with improved disease outcome in patients affected by a variety of neoplasms, with the notable exception of multiple myeloma (MM). Here, we describe an optimized protocol for the flow cytometry-assisted quantification of surface-exposed CALR and PS on CD38 plasma cells from the bone marrow of patients with MM. With some variations, we expect this method to be straightforwardly adaptable to the detection of CALR and PS on the surface of cancer cells isolated from patients with neoplasms other than MM.

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Source
http://dx.doi.org/10.1016/bs.mcb.2024.05.009DOI Listing

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