Dynamics of the immune status in patients with cervical cancer receiving complex treatment with dendritic cell vaccine.
ABSTRACT
Background: The purpose of the study was to determine the influence of complex treatment with dendritic cell vaccine on the dynamics of the immune status of patients with cervical cancer.
Methods: 17 patients with cervical cancer (CC) T2b-4аN0-1M0-1 received chemotherapy with combined radiotherapy to the pelvic area. Between courses of cytostatic treatment, patients underwent dendritic cell vaccination (DCV) planned individually depending on the treatment effect, which was evaluated by the results of examination, US, CT and MRI. A control group included 19 patients with locally advanced CC receiving standard polychemotherapy (PCT) and radiotherapy. Immune status of patients was evaluated by flow cytometry (FACSCantoII BD) including T, B, NK cells, Tregs (CD4+CD25+CD127dim), memory T cells (Тm) and naïve T lymphocytes (Th0) was determined in the dynamics of the treatment. Results were calculated as a percentage from the total number of lymphocytes, for Tregs – in % from CD3+CD4+ cells, for Тm and Th0 – in % from CD3+CD4+ and CD3+CD8+ cells.
Results: 1 to 4 cycles of PCT with DCV caused a transient increase in Tregs after the 1st cycle, with further regression to the initial levels; other studied lymphocyte subsets remained unchanged. Only after 8 or more DCV cycles, a favorable immunological dynamics developed; however, it was not observed in controls. DCV increased levels of lymphocytes with potential cytotoxicity: CD3+CD8+ (from 19.0±2.0 to 28.8±1.5%), NK cells (from 12.0±2.0 to 21.2±1.9%). During DCV courses helper-inducer Tm amount rose from 51.7±6.3 to 69.7±4.3%, while in remission – CD8+Tm grew from 28.5±2.1 to 40.4±5.3% (p < 0.05 for all cases). Repeated DCV was satisfactorily tolerated by CC patients and, when used in complex treatment, caused a pronounced clinical effect. DCV did not lead to serious adverse events. Patients in remission are still observed.
Conclusions: Treatment for CC with DCV causes a positive dynamics of the immune status, with the maximal effect after 8 and more DCV cycles. Remission is apparently maintained due to an increase in the level of TmCD8+ cells.