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1.
Nat Commun ; 11(1): 6299, 2020 12 07.
Article in English | MEDLINE | ID: mdl-33288764

ABSTRACT

Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E2 release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E2 biosythesis favors CD103+ dendritic cell activation that primes a Tc1-polarized CD8+ T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E2 blockade as a strategy to harness ICD.


Subject(s)
Alarmins/metabolism , Antineoplastic Agents/pharmacology , Dinoprostone/metabolism , Immunogenic Cell Death/drug effects , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Calreticulin/metabolism , Cell Line, Tumor , Cisplatin/pharmacology , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , HMGB1 Protein/metabolism , Humans , Immunization/methods , Mice, Inbred C57BL , Gemcitabine
2.
Klin Lab Diagn ; (1): 17-20, 2008 Jan.
Article in Russian | MEDLINE | ID: mdl-18314774

ABSTRACT

Multiple myeloma is a malignant proliferative disease of plasma cells. Flow cytometric immunophenotyping makes it possible to identify a malignant clone of myeloma cells in the shortest possible time, to determine its phenotype, and differentiate transformed and preserved plasma cells. The article presents an immunophenotyping strategy using three-color monoclonal antibodies (CD35, CD14, CD38, CD138, and CD19) and an algorithm of verification of transformed plasma cells. Particular emphasis is placed on both the practical aspects of performing this assay and on the clinical application of the obtained results.


Subject(s)
Antigens, CD/analysis , Bone Marrow/immunology , Immunophenotyping/methods , Multiple Myeloma/diagnosis , Antibodies, Monoclonal/immunology , Bone Marrow/pathology , Flow Cytometry/methods , Humans , Multiple Myeloma/pathology
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