Prostate Cancer Survivors Present Long-Term, Residual Systemic Immune Alterations.

Abstract

Simple SummaryThe development of cancer is very often accompanied by systemic immune alterations which can be further aggravated by major anti-cancer therapies. However, there is very little known about how long these alterations persist in patients successfully cured of cancer. The aim of our work was to investigate how cancer and radiotherapy as major anti-cancer treatment modalities impact the immune system long after the successful treatment of a tumor. We investigated prostate cancer patients treated with a special form of radiotherapy (low-dose rate brachytherapy) often used for the treatment of prostate cancer and followed a wide range of immune parameters at regular intervals up to 3 years after the start of the treatment. Our results showed that some immune alterations did not recover after the treatment of the disease, on the contrary, they persisted, and in some cases got even worse. Further studies are needed to explain the causes and the potential long-term consequences of these alterations. Background: The development of cancer and anti-tumor therapies can lead to systemic immune alterations but little is known about how long immune dysfunction persists in cancer survivors. Methods: We followed changes in the cellular immune parameters of prostate cancer patients with good prognostic criteria treated with low dose rate brachytherapy before and up to 3 years after the initiation of therapy. Results: Patients before therapy had a reduced CD4+ T cell pool and increased regulatory T cell fraction and these alterations persisted or got amplified during the 36-month follow-up. A significant decrease in the total NK cell number and a redistribution of the circulating NK cells in favor of a less functional anergic subpopulation was seen in patients before therapy but tumor regression led to the regeneration of the NK cell pool and functional integrity. The fraction of lymphoid DCs was increased in patients both before therapy and throughout the whole follow-up. Increased PDGF-AA, BB, CCL5 and CXCL5 levels were measured in patients before treatment but protein levels rapidly normalized. Conclusions: while NK cell dysfunction recovered, long-term, residual alterations persisted in the adaptive and partly in the innate immune system.