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Cytoskeletal dynamics and mitochondrial rearrangements drive cell fate upon antibody-induced complement activation in DLBCL
by
Breij, Esther C. W.
, Csikós, Tamás
, de Lint, Klaas
, Roukens, M. Guy
, Quik, Marjolein
, van der Schans, Jort J.
, Karagoz, Kubra
, Santegoets, Kim C. M.
, Overdijk, Marije B.
, van der Horst, Hilma J.
, Chamuleau, Martine E. D.
, Guan, Meijian
, Nuñez Moreno, Gonzalo
, Mutis, Tuna
in
631/250/251
/ 631/250/262
/ 631/67/1059/2326
/ 631/67/1059/602
/ 631/67/1990/291/1621/1915
/ Actins - metabolism
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ Cancer Research
/ Cell death
/ Cell Line, Tumor
/ Complement Activation - drug effects
/ Complement Activation - immunology
/ Cytoskeleton - immunology
/ Cytoskeleton - metabolism
/ Cytotoxicity
/ Flow cytometry
/ Genes
/ Hematology
/ Humans
/ Lymphatic system
/ Lymphoma
/ Lymphoma, Large B-Cell, Diffuse - drug therapy
/ Lymphoma, Large B-Cell, Diffuse - immunology
/ Lymphoma, Large B-Cell, Diffuse - metabolism
/ Lymphoma, Large B-Cell, Diffuse - pathology
/ Medical research
/ Mitochondria - immunology
/ Mitochondria - metabolism
/ Mitochondria - pathology
/ Mitophagy
/ Morphology
/ Oncology
/ Patients
/ Proteins
/ Reactive Oxygen Species - metabolism
2025
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Cytoskeletal dynamics and mitochondrial rearrangements drive cell fate upon antibody-induced complement activation in DLBCL
by
Breij, Esther C. W.
, Csikós, Tamás
, de Lint, Klaas
, Roukens, M. Guy
, Quik, Marjolein
, van der Schans, Jort J.
, Karagoz, Kubra
, Santegoets, Kim C. M.
, Overdijk, Marije B.
, van der Horst, Hilma J.
, Chamuleau, Martine E. D.
, Guan, Meijian
, Nuñez Moreno, Gonzalo
, Mutis, Tuna
in
631/250/251
/ 631/250/262
/ 631/67/1059/2326
/ 631/67/1059/602
/ 631/67/1990/291/1621/1915
/ Actins - metabolism
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ Cancer Research
/ Cell death
/ Cell Line, Tumor
/ Complement Activation - drug effects
/ Complement Activation - immunology
/ Cytoskeleton - immunology
/ Cytoskeleton - metabolism
/ Cytotoxicity
/ Flow cytometry
/ Genes
/ Hematology
/ Humans
/ Lymphatic system
/ Lymphoma
/ Lymphoma, Large B-Cell, Diffuse - drug therapy
/ Lymphoma, Large B-Cell, Diffuse - immunology
/ Lymphoma, Large B-Cell, Diffuse - metabolism
/ Lymphoma, Large B-Cell, Diffuse - pathology
/ Medical research
/ Mitochondria - immunology
/ Mitochondria - metabolism
/ Mitochondria - pathology
/ Mitophagy
/ Morphology
/ Oncology
/ Patients
/ Proteins
/ Reactive Oxygen Species - metabolism
2025
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Cytoskeletal dynamics and mitochondrial rearrangements drive cell fate upon antibody-induced complement activation in DLBCL
by
Breij, Esther C. W.
, Csikós, Tamás
, de Lint, Klaas
, Roukens, M. Guy
, Quik, Marjolein
, van der Schans, Jort J.
, Karagoz, Kubra
, Santegoets, Kim C. M.
, Overdijk, Marije B.
, van der Horst, Hilma J.
, Chamuleau, Martine E. D.
, Guan, Meijian
, Nuñez Moreno, Gonzalo
, Mutis, Tuna
in
631/250/251
/ 631/250/262
/ 631/67/1059/2326
/ 631/67/1059/602
/ 631/67/1990/291/1621/1915
/ Actins - metabolism
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Biopsy
/ Cancer Research
/ Cell death
/ Cell Line, Tumor
/ Complement Activation - drug effects
/ Complement Activation - immunology
/ Cytoskeleton - immunology
/ Cytoskeleton - metabolism
/ Cytotoxicity
/ Flow cytometry
/ Genes
/ Hematology
/ Humans
/ Lymphatic system
/ Lymphoma
/ Lymphoma, Large B-Cell, Diffuse - drug therapy
/ Lymphoma, Large B-Cell, Diffuse - immunology
/ Lymphoma, Large B-Cell, Diffuse - metabolism
/ Lymphoma, Large B-Cell, Diffuse - pathology
/ Medical research
/ Mitochondria - immunology
/ Mitochondria - metabolism
/ Mitochondria - pathology
/ Mitophagy
/ Morphology
/ Oncology
/ Patients
/ Proteins
/ Reactive Oxygen Species - metabolism
2025
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Cytoskeletal dynamics and mitochondrial rearrangements drive cell fate upon antibody-induced complement activation in DLBCL
Journal Article
Cytoskeletal dynamics and mitochondrial rearrangements drive cell fate upon antibody-induced complement activation in DLBCL
2025
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Overview
Complement-dependent cytotoxicity (CDC) is an important effector function of various therapeutic antibodies. Cancer resistance to CDC is primarily attributed to extracellular factors. Using diffuse large B-cell lymphoma (DLBCL) models, we elucidated intracellular evasion mechanisms. By CRISPR-Cas9 library screening, we identified mitochondrial damage and reactive oxygen species as the key intracellular drivers of CDC. CDC resistance was linked to augmented mitochondrial mass, elongated mitochondria and reduced mitophagy, and decreased expression of actin-related genes. Actin downregulation in CDC-resistant cells occurred specifically within the mitochondria, connecting mitochondrial rearrangements and cytoskeletal dynamics with resistance. Stimulating actin polymerization could partially overcome CDC resistance. Of clinical significance, we observed a positive association between the cytoskeleton and antibody responses in DLBCL patient samples. In conclusion, our study unveils novel intracellular resistance mechanisms to antibody-induced CDC, highlighting the critical roles of mitochondrial rearrangements and cytoskeletal dynamics in CDC. We propose that decreased mitochondrial actin prevents overload of the mitophagy pathway, thereby reducing CDC.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Biopsy
/ Complement Activation - drug effects
/ Complement Activation - immunology
/ Genes
/ Humans
/ Lymphoma
/ Lymphoma, Large B-Cell, Diffuse - drug therapy
/ Lymphoma, Large B-Cell, Diffuse - immunology
/ Lymphoma, Large B-Cell, Diffuse - metabolism
/ Lymphoma, Large B-Cell, Diffuse - pathology
/ Oncology
/ Patients
/ Proteins
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