TY - JOUR
T1 - Brachytherapy for targeting the immune system in cervical cancer patients
AU - Linares, Isabel
AU - Berenguer Frances, Miguel Ángel
AU - Cañas, Rut
AU - Najjari, Dina
AU - Gutiérrez, Cristina
AU - Marín, Susanna
AU - Comas, Silvia
AU - Guedea, Ferran
AU - Pujol Canadell, Mònica
PY - 2023
Y1 - 2023
N2 - New combinations based on standard therapeutic modalities and immunotherapy require understanding the immunomodulatory properties of traditional treatments. The objective was to evaluate the impact of brachytherapy (BT) on the immune system of cervical cancer and to identify the best modality, High-dose-rate brachytherapy (HDR-BT) vs. Pulsed-dose-rate (PDR-BT), to target it. Nineteen patients enrolled in a prospective study received chemoradiation (CRT) and subsequently HDR-BT or PDR-BT. Peripheral blood samples were obtained for immunophenotyping analysis by flow-cytometry before CRT, BT, and two and four weeks after BT. The Friedman one-way ANOVA, Conover post hoc test, and the Wilcoxon signed-rank test were used to compare changes in cell populations at different periods, perform multiple pairwise comparisons and assess differences between treatment groups (PDR and HDR). Natural killer cells (NKs) were the best target for BT. Patients receiving HDR-BT achieved significantly higher values and longer time of the CD56dimCD16 + NK cells with greater cytotoxic capacity than the PDR-BT group, which presented their highest elevation of CD56-CD16 + NK cells. Furthermore, both BT modalities were associated with an increase in myeloid-derived suppressor cells (MDSCs), related to a worse clinical prognosis. However, there was a decrease in the percentage of CD4 + CD25 + Foxp3 + CD45RA + regulatory T cells (Tregs) in patients receiving HDR-BT, although there were no significant differences between BT. Immune biomarkers are important predictive determinants in cervical cancer. Higher cytotoxic NK cells and a trend toward lower values of Tregs might support the use of HDR-BT to the detriment of PDR-BT and help develop effective combinations with immunotherapy. The online version contains supplementary material available at 10.1186/s12865-023-00559-y.
AB - New combinations based on standard therapeutic modalities and immunotherapy require understanding the immunomodulatory properties of traditional treatments. The objective was to evaluate the impact of brachytherapy (BT) on the immune system of cervical cancer and to identify the best modality, High-dose-rate brachytherapy (HDR-BT) vs. Pulsed-dose-rate (PDR-BT), to target it. Nineteen patients enrolled in a prospective study received chemoradiation (CRT) and subsequently HDR-BT or PDR-BT. Peripheral blood samples were obtained for immunophenotyping analysis by flow-cytometry before CRT, BT, and two and four weeks after BT. The Friedman one-way ANOVA, Conover post hoc test, and the Wilcoxon signed-rank test were used to compare changes in cell populations at different periods, perform multiple pairwise comparisons and assess differences between treatment groups (PDR and HDR). Natural killer cells (NKs) were the best target for BT. Patients receiving HDR-BT achieved significantly higher values and longer time of the CD56dimCD16 + NK cells with greater cytotoxic capacity than the PDR-BT group, which presented their highest elevation of CD56-CD16 + NK cells. Furthermore, both BT modalities were associated with an increase in myeloid-derived suppressor cells (MDSCs), related to a worse clinical prognosis. However, there was a decrease in the percentage of CD4 + CD25 + Foxp3 + CD45RA + regulatory T cells (Tregs) in patients receiving HDR-BT, although there were no significant differences between BT. Immune biomarkers are important predictive determinants in cervical cancer. Higher cytotoxic NK cells and a trend toward lower values of Tregs might support the use of HDR-BT to the detriment of PDR-BT and help develop effective combinations with immunotherapy. The online version contains supplementary material available at 10.1186/s12865-023-00559-y.
KW - Immune system
KW - Cervical cancer
KW - Brachytherapy, Flow cytometry
KW - Natural killer cells
KW - Immunosuppressive cells
UR - https://www.scopus.com/pages/publications/85167528230
U2 - 10.1186/s12865-023-00559-y
DO - 10.1186/s12865-023-00559-y
M3 - Article
C2 - 37559025
SN - 1471-2172
VL - 24
JO - BMC Immunology
JF - BMC Immunology
ER -