Premortem autophagy determines the immunogenicity of chemotherapy-induced cancer cell death |
| |
Authors: | Chandini M Thirukkumaran Zhong Qiao Shi Joanne Luider Karen Kopciuk He Gao Nizar Bahlis Paola Neri Mark Pho Doug Stewart Adnan Mansoor Don G Morris |
| |
Institution: | 1.Department of Oncology; University of Calgary; Calgary, Alberta CA;2.Tom Baker Cancer Center; Calgary, Alberta CA;3.Calgary Laboratory Services; Calgary, Alberta CA;4.Department of Public Health Sciences; School of Public Health; University of Alberta; Edmonton, Alberta CA |
| |
Abstract: | Multiple myeloma (MM) is a clonal plasma cell malignancy that accounts for 10–15% of newly diagnosed hematological cancers. Although significant advances have been made in the treatment of MM the disease still remains incurable. The oncolytic potential of reovirus has previously been demonstrated by others and us and is currently in phase III clinical trials for solid tumors. In addition a phase I clinical trial has recently been initiated for MM. Despite the clinical activity, the mechanism(s) of cell death caused by reovirus in MM is yet not well elucidated. A comprehensive understanding of reovirus-mediated histology-specific cell death mechanisms is imperative if this therapeutic is to become a standard of care for patients. Previously we have shown that reovirus-mediated cell death of breast and prostate cancer is orchestrated via apoptosis. The present study demonstrates for the first time that in addition to inducing apoptosis reovirus also upregulates autophagy during oncolysis of MM. |
| |
Keywords: | apyrases Atg5 Beclin 1 calreticulin HMGB1 immunogenic cell death |
|