The ever-expanding immunomodulatory role of calreticulin in cancer immunity.
de Bruyn, M
Frontiers in Oncology
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Calreticulin is a pleiotropic molecule that normally resides in the lumen of the endoplasmic reticulum (ER). Here, it has various functions, ranging from regulation of calcium homeostasis to ensuring proper protein folding. More recently, calreticulin gained special interest for its extracellular functions, where it has direct immunomodulatory activity. In this respect, calreticulin activates dendritic cells and macrophages. In addition, certain anti-cancer therapies induce the translocation of calreticulin from the ER to the cell surface of dying cancer cells, where calreticulin dictates the immunogenicity of these cells. Interestingly, treatment with tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) also induces membrane calreticulin exposure on cancer cells. As shown here, calreticulin directly interacts with TRAIL and its receptor-signaling complex, as well as with other TNF family members. Of note, TRAIL is a well known immunomodulatory molecule, and is expressed on the surface of natural killer T-cells. Therefore, calreticulin may have an as yet unrecognized wide(r) impact on immunity, with the TNF-ligand family modulating virtually all aspects of the immune response.
Dutch Cancer Society
Netherlands Organization for Scientific Research
European Communities Seventh Framework Programme (FP7/2007-2013)
This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.
Frontiers in Oncology, 2015, Vol. 5, Issue 35
RUG 2009-4355 (EB), RUG2009-4542, RUG2011-5206, RUG2012-5541, RUG2013-6209
215009 RedCat (PE)
Place of publication