Impact of curative radiotherapy on the immune status of patients with localized prostate cancer

Oncoimmunology. 2018 Aug 27;7(11):e1496881. doi: 10.1080/2162402X.2018.1496881. eCollection 2018.

Abstract

Combination of radiotherapy with immunotherapy has become an attractive concept for the treatment of cancer. The objective of this study was to assess the effect of curative, normofractionated radiotherapy on peripheral immune lymphocytes in prostate cancer patients, in order to propose a rationale for scheduling of normofractionated radiotherapy with T-cell based immunotherapy. In a prospective study (clinicaltrials.gov: NCT01376674), eighteen patients with localized prostate cancer were treated with radiotherapy with or without hormonal therapy. Irradiation volumes encompassed prostate and, in select cases, elective pelvic nodal regions. Blood samples were collected from all patients before, during, and after radiotherapy, as well as from 6 healthy individuals as control. Normofractionated radiotherapy of prostate cancer over eight weeks had a significant influence on the systemic immune status of patients compared to healthy controls. Absolute leukocyte and lymphocyte counts decreased during treatment as did peripheral blood immune subsets (T cells, CD8+ and naïve CD4+ T cells, B cells). Regulatory T cells and NK cells increased. Proliferation of all immune cells except regulatory T cells increased during RT. Most of these changes were transient. Importantly, the functionality of T lymphocytes and the frequency of antigen-specific CD8+ T cells were not affected during therapy. Our data indicate that combination of normofractionated radiotherapy with immunotherapy might be feasible for patients with prostate cancer. Conceptually, beginning with immunotherapy early during the course of radiotherapy could be beneficial, as the percentage of T cells is highest, the percentage of regulatory T cells is lowest, and as the effects of radiotherapy did not completely subside 3 months after end of radiotherapy.

Keywords: Prostate cancer; T cells; immunotherapy; peripheral lymphocytes; radiotherapy.

Associated data

  • ClinicalTrials.gov/NCT01376674

Grant support

This work was supported by the Medical Faculty of Tuebingen under Grant 261-0-0. Franziska Eckert was partly supported by the Else-Kroener-Fresenius Research Foundation under Grant 2015_Kolleg.14. Philipp Schaedle was supported by the Studienstiftung des Deutschen Volkes. Cihan Gani was partly supported by the Clinician Scientist Program of the Medical faculty of Tuebingen under grant 363-0-0. Cécile Gouttefangeas and Hans-Georg Rammensee were supported by the Deutsche Forschungsgemeinschaft (SFB685) and Hans-Georg Rammensee holds an ERC Advanced Grant (Mutaediting; 339842).