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Association of cell death markers with tumor immune cell infiltrates after chemo-radiation in cervical cancer

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Abstract
Irradiation induces distinct cellular responses such as apoptosis, necroptosis, iron-dependent cell death (a feature of ferroptosis), senescence, and mitotic catastrophe. Several of these outcomes are immunostimulatory and may represent a potential for immunogenic type of cell death (ICD) induced by radiotherapy triggering abscopal effects. The purpose of this study is to determine whether intra-tumoral ICD markers can serve as biomarkers for the prediction of patient's outcomes defined as the metastasis status and survival over a 5-year period. Thirty-eight patients with locally advanced cervical cancer, treated with neoadjuvant chemoradiotherapy using cisplatin were included in this study. Pre-treatment tumor biopsy and post-treatment hysterectomy samples were stained for cell death markers and danger associated molecular patterns (DAMPs): cleaved caspase-3 (apoptosis), phosphorylated mixed lineage kinase domain like pseudokinase (pMLKL; necroptosis), glutathione peroxidase 4 (GPX4; ferroptosis) and 4-hydroxy-2-noneal (4-HNE; ferroptosis), high mobility group box 1 (HMGB1) and calreticulin. Although these markers could not predict the patient's outcome in terms of relapse or survival, many significantly correlated with immune cell infiltration. For instance, inducing ferroptosis post-treatment seems to negatively impact immune cell recruitment. Measuring ICD markers could reflect the impact of treatment on the tumor microenvironment with regard to immune cell recruitment and infiltration. One Sentence SummaryCell death readouts during neoadjuvant chemoradiation in cervical cancer
Keywords
Cancer Research, Oncology, cervical cancer, biomarkers, immunogenic cell death, cell death, tumor infiltrating leucocytes, MODULATED ARC THERAPY, NECROPTOSIS, CHEMORADIOTHERAPY, OVEREXPRESSION, RADIOTHERAPY, CARCINOMA, OUTCOMES, DAMAGE, MLKL

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MLA
Oltean, Teodora-Eugenia, et al. “Association of Cell Death Markers with Tumor Immune Cell Infiltrates after Chemo-Radiation in Cervical Cancer.” FRONTIERS IN ONCOLOGY, vol. 12, 2022, doi:10.3389/fonc.2022.892813.
APA
Oltean, T.-E., Lippens, L., Lemeire, K., De Tender, C., Vuylsteke, M., Denys, H., … Adjemian Catani, S. (2022). Association of cell death markers with tumor immune cell infiltrates after chemo-radiation in cervical cancer. FRONTIERS IN ONCOLOGY, 12. https://doi.org/10.3389/fonc.2022.892813
Chicago author-date
Oltean, Teodora-Eugenia, Lien Lippens, Kelly Lemeire, Caroline De Tender, Marnik Vuylsteke, Hannelore Denys, Katrien Vandecasteele, Peter Vandenabeele, and Sandy Adjemian Catani. 2022. “Association of Cell Death Markers with Tumor Immune Cell Infiltrates after Chemo-Radiation in Cervical Cancer.” FRONTIERS IN ONCOLOGY 12. https://doi.org/10.3389/fonc.2022.892813.
Chicago author-date (all authors)
Oltean, Teodora-Eugenia, Lien Lippens, Kelly Lemeire, Caroline De Tender, Marnik Vuylsteke, Hannelore Denys, Katrien Vandecasteele, Peter Vandenabeele, and Sandy Adjemian Catani. 2022. “Association of Cell Death Markers with Tumor Immune Cell Infiltrates after Chemo-Radiation in Cervical Cancer.” FRONTIERS IN ONCOLOGY 12. doi:10.3389/fonc.2022.892813.
Vancouver
1.
Oltean T-E, Lippens L, Lemeire K, De Tender C, Vuylsteke M, Denys H, et al. Association of cell death markers with tumor immune cell infiltrates after chemo-radiation in cervical cancer. FRONTIERS IN ONCOLOGY. 2022;12.
IEEE
[1]
T.-E. Oltean et al., “Association of cell death markers with tumor immune cell infiltrates after chemo-radiation in cervical cancer,” FRONTIERS IN ONCOLOGY, vol. 12, 2022.
@article{8762757,
  abstract     = {{Irradiation induces distinct cellular responses such as apoptosis, necroptosis, iron-dependent cell death (a feature of ferroptosis), senescence, and mitotic catastrophe. Several of these outcomes are immunostimulatory and may represent a potential for immunogenic type of cell death (ICD) induced by radiotherapy triggering abscopal effects. The purpose of this study is to determine whether intra-tumoral ICD markers can serve as biomarkers for the prediction of patient's outcomes defined as the metastasis status and survival over a 5-year period. Thirty-eight patients with locally advanced cervical cancer, treated with neoadjuvant chemoradiotherapy using cisplatin were included in this study. Pre-treatment tumor biopsy and post-treatment hysterectomy samples were stained for cell death markers and danger associated molecular patterns (DAMPs): cleaved caspase-3 (apoptosis), phosphorylated mixed lineage kinase domain like pseudokinase (pMLKL; necroptosis), glutathione peroxidase 4 (GPX4; ferroptosis) and 4-hydroxy-2-noneal (4-HNE; ferroptosis), high mobility group box 1 (HMGB1) and calreticulin. Although these markers could not predict the patient's outcome in terms of relapse or survival, many significantly correlated with immune cell infiltration. For instance, inducing ferroptosis post-treatment seems to negatively impact immune cell recruitment. Measuring ICD markers could reflect the impact of treatment on the tumor microenvironment with regard to immune cell recruitment and infiltration. One Sentence SummaryCell death readouts during neoadjuvant chemoradiation in cervical cancer}},
  articleno    = {{892813}},
  author       = {{Oltean, Teodora-Eugenia and Lippens, Lien and Lemeire, Kelly and De Tender, Caroline and Vuylsteke, Marnik and Denys, Hannelore and Vandecasteele, Katrien and Vandenabeele, Peter and Adjemian Catani, Sandy}},
  issn         = {{2234-943X}},
  journal      = {{FRONTIERS IN ONCOLOGY}},
  keywords     = {{Cancer Research,Oncology,cervical cancer,biomarkers,immunogenic cell death,cell death,tumor infiltrating leucocytes,MODULATED ARC THERAPY,NECROPTOSIS,CHEMORADIOTHERAPY,OVEREXPRESSION,RADIOTHERAPY,CARCINOMA,OUTCOMES,DAMAGE,MLKL}},
  language     = {{eng}},
  pages        = {{12}},
  title        = {{Association of cell death markers with tumor immune cell infiltrates after chemo-radiation in cervical cancer}},
  url          = {{http://doi.org/10.3389/fonc.2022.892813}},
  volume       = {{12}},
  year         = {{2022}},
}

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