Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3
<b>Background:</b> Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies. Moreover, immunotherapeutic s...
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2024-12-01
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| author | Elizabeth Schmitz Abigail Ridout Audrey L. Smith Alexandria P. Eiken Sydney A. Skupa Erin M. Drengler Sarbjit Singh Sandeep Rana Amarnath Natarajan Dalia El-Gamal |
| author_facet | Elizabeth Schmitz Abigail Ridout Audrey L. Smith Alexandria P. Eiken Sydney A. Skupa Erin M. Drengler Sarbjit Singh Sandeep Rana Amarnath Natarajan Dalia El-Gamal |
| author_sort | Elizabeth Schmitz |
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| description | <b>Background:</b> Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies. Moreover, immunotherapeutic success in CLL has been stifled by its pro-tumor microenvironment milieu and low mutational burden, cultivating poor antigenicity and limited ability to generate anti-tumor immunity through adaptive immune cell engagement. Previously, we have demonstrated how a three-carbon-linker spirocyclic dimer (SpiD3) promotes futile activation of the unfolded protein response (UPR) in CLL cells through immense misfolded-protein mimicry, culminating in insurmountable ER stress and programmed CLL cell death. <b>Method:</b> Herein, we used flow cytometry and cell-based assays to capture the kinetics and magnitude of SpiD3-induced damage-associated molecular patterns (DAMPs) in CLL cell lines and primary samples. <b>Result:</b> SpiD3 treatment, <i>in vitro</i> and <i>in vivo</i>, demonstrated the capacity to propagate immunogenic cell death through emissions of classically immunogenic DAMPs (CALR, ATP, HMGB1) and establish a chemotactic gradient for bone marrow-derived dendritic cells. <b>Conclusions:</b> Thus, this study supports future investigation into the relationship between novel therapeutics, manners of cancer cell death, and their contributions to adaptive immune cell engagement as a means for improving anti-cancer therapy in CLL. |
| format | Article |
| id | doaj-art-5b9c3bb917914cc38abf7edbcf65fa0f |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-5b9c3bb917914cc38abf7edbcf65fa0f2024-12-27T14:13:04ZengMDPI AGBiomedicines2227-90592024-12-011212285710.3390/biomedicines12122857Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3Elizabeth Schmitz0Abigail Ridout1Audrey L. Smith2Alexandria P. Eiken3Sydney A. Skupa4Erin M. Drengler5Sarbjit Singh6Sandeep Rana7Amarnath Natarajan8Dalia El-Gamal9Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USAEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA<b>Background:</b> Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies. Moreover, immunotherapeutic success in CLL has been stifled by its pro-tumor microenvironment milieu and low mutational burden, cultivating poor antigenicity and limited ability to generate anti-tumor immunity through adaptive immune cell engagement. Previously, we have demonstrated how a three-carbon-linker spirocyclic dimer (SpiD3) promotes futile activation of the unfolded protein response (UPR) in CLL cells through immense misfolded-protein mimicry, culminating in insurmountable ER stress and programmed CLL cell death. <b>Method:</b> Herein, we used flow cytometry and cell-based assays to capture the kinetics and magnitude of SpiD3-induced damage-associated molecular patterns (DAMPs) in CLL cell lines and primary samples. <b>Result:</b> SpiD3 treatment, <i>in vitro</i> and <i>in vivo</i>, demonstrated the capacity to propagate immunogenic cell death through emissions of classically immunogenic DAMPs (CALR, ATP, HMGB1) and establish a chemotactic gradient for bone marrow-derived dendritic cells. <b>Conclusions:</b> Thus, this study supports future investigation into the relationship between novel therapeutics, manners of cancer cell death, and their contributions to adaptive immune cell engagement as a means for improving anti-cancer therapy in CLL.https://www.mdpi.com/2227-9059/12/12/2857chronic lymphocytic leukemia (CLL)SpiD3immunogenic cell death (ICD)damage-associated molecular patterns (DAMPs)ferroptosisoxidative stress |
| spellingShingle | Elizabeth Schmitz Abigail Ridout Audrey L. Smith Alexandria P. Eiken Sydney A. Skupa Erin M. Drengler Sarbjit Singh Sandeep Rana Amarnath Natarajan Dalia El-Gamal Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3 Biomedicines chronic lymphocytic leukemia (CLL) SpiD3 immunogenic cell death (ICD) damage-associated molecular patterns (DAMPs) ferroptosis oxidative stress |
| title | Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3 |
| title_full | Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3 |
| title_fullStr | Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3 |
| title_full_unstemmed | Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3 |
| title_short | Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3 |
| title_sort | immunogenic cell death traits emitted from chronic lymphocytic leukemia cells following treatment with a novel anti cancer agent spid3 |
| topic | chronic lymphocytic leukemia (CLL) SpiD3 immunogenic cell death (ICD) damage-associated molecular patterns (DAMPs) ferroptosis oxidative stress |
| url | https://www.mdpi.com/2227-9059/12/12/2857 |
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