Brachytherapy for prostate cancer and immune response.

Abstract

Introduction. Information about the brachytherapy-induced immune reactions, which can be used for therapeutic purposes, is of great clinical value. Materials and methods. When preparing a review of the literature on the problem of the effect of brachytherap (BT) on immunity in prostate cancer (PCa), the following bibliographic databases were used: PubMed, Science Direct, Scientific Electronic Library of Russia (eLibrary). The search was conducted on the following keywords: «cancer», «prostate cancer», «brachytherapy», «immunity», «immunotherapy». In total, 6 sources were found that were directly related to the effect of BT on immunity in prostate cancer. Results. Clinical data shows that both low-dose and high-dose prostate cancer brachytherapy (BT) cause a systemic immune response. The authors explain the observed increase in the number of serum leukocytes by the induction of an inflammatory reaction in response to tumor irradiation, and the decrease in the number of B cells by the movement of antigen-recognizing B cells from the bloodstream to the irradiation site. In addition, after BT, an increase in the number of activated T-lymphocytes was demonstrated, while the number of myeloid suppressor cells significantly decreased. It has been suggested that a decrease in this indicator can activate T cells: the number of naive CD4+ and CD8+ T lymphocytes significantly increased after local administration of radioactive sources, with a simultaneous decrease in the number of CD4+ and CD8+ memory T cells. The latter may indicate that local radiotherapy stimulates the activation of the thymus and the release of naive T-lymphocytes into the bloodstream, during the migration of memory cells from the bloodstream to the prostate. The described effects reflect the process of «turning on» T-cell immunity after BT. Researchers believe that an increase in the number of activated T-lymphocytes contributes to the activation of antitumor immunity, long-term remission and reduces the likelihood of recurrence of prostate cancer. High-dose BT of localized prostate cancer, as well as probably low-dose BT, cause the transformation of the immunogenic properties of the tumor and lead to pronounced polyclonal infiltration of the prostate, mainly by T cells, which occurs under the control of a large number of «control points». The occurrence of immune cells infiltrates and changes in the signal transmission system between them after BT are reflected by a change in the type of «inflammatory signature of the tumor» (TIS) from «cold» to «hot». After irradiation in the tumor area the number of PD-L1 macrophages usually increases, which is regarded as a marker of the tumor response to the therapy. It is believed that if BT causes an increase in PD1+ expression, and use of checkpoint inhibitors to these patients can give a good therapeutic effect. Conclusion. The available data indicate that BT primes the systemic immune response, leads to activation of T-cell immunity and, as a consequence, antitumor immunity. All this opens up prospects for the development of prostate cancer combined treatment methods, using BT and immunotherapy.