title: Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome.
abstract: Background. Apoptotic rates in peripheral blood lymphocytes can predict radiation induced normal tissue toxicity. We studied whether apoptosis in lymphocytes has a prognostic value for therapy outcome. Methods. Lymphocytes of 87 rectal cancer patients were ex vivo irradiated with 2 Gy, 8 Gy, or a combination of 2 Gy ionizing radiation and Oxaliplatin. Cells were stained with Annexin V and 7-Aminoactinomycin D and apoptotic and necrotic rates were analyzed by multicolor flow cytometry. Results. After treatment, apoptotic and necrotic rates in CD8+ cells are consistently higher than in CD4+ cells, with lower corresponding necrotic rates. Apoptotic and necrotic rates of CD4+ cells and CD8+ cells correlated well within the 2 Gy, 8 Gy, and 2 Gy and Oxaliplatin arrangements (p ≤ 0.009). High apoptotic CD8+ rates after 2 Gy, 8 Gy, and 2 Gy + Oxaliplatin treatment were prognostically favorable for metastasis-free survival (p = 0.009, p = 0.038, and p = 0.009) and disease-free survival (p = 0.013, p = 0.098, and p = 0.013). Conclusions. Ex vivo CD8+ apoptotic rates are able to predict the patient outcome in regard to metastasis-free or disease-free survival. Patients with higher CD8+ apoptotic rates in the peripheral blood have a more favorable prognosis. In addition to the prediction of late-toxicity by utilization of CD4+ apoptotic rates, the therapy outcome can be predicted by CD8+ apoptotic rates.
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Sebastian
authors.identifier: 0000-0001-8570-3482
authors.initials: S
authors.lastname: Winkler
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Philipp
authors.identifier: 0000-0002-1467-5696
authors.initials: P
authors.lastname: Hoppe
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Marlen
authors.initials: M
authors.lastname: Haderlein
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Markus
authors.identifier: 0000-0003-2082-216X
authors.initials: M
authors.lastname: Hecht
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Rainer
authors.identifier: 0000-0001-8295-7145
authors.initials: R
authors.lastname: Fietkau
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen and Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Luitpold V
authors.identifier: 0000-0002-8040-3226
authors.initials: LV
authors.lastname: Distel