Immunomodulatory effects of carbon ion radiotherapy in patients with localized prostate cancer

Abstract

Purpose Radiotherapy is one of the main local treatment modalities for prostate cancer, while immunosuppressive effect induced by radiotherapy is an important factor of radiation resistance and treatment failure. Carbon ion radiotherapy (CIRT) is a novel radiotherapy technique and the immunomodulatory effect of CIRT provides the possibility of overcoming radioresistance and improving efficacy. The aim of this study was to assess the immune response evoked by CIRT in localized prostate cancer patients. Methods Thirty-two patients were treated by CIRT combined with or without hormone therapy and peripheral blood samples were collected before and after CIRT. Investigation of peripheral immune cell frequency, proliferation, and cytokine expression was conducted by flow cytometry, real-time quantitative PCR and ELISA. Results There were no significant differences in the frequencies of CD3 + , CD4 + , CD8 + T cells and NK cells after CIRT. CD4/CD8 ratio increased whereas B cells decreased. All lymphocyte subsets except regulatory T cells (Tregs) displayed increased proliferation and T cells exhibited increased functionality after CIRT, characterized by modestly increased cytokine secretion of TNF. Moreover, higher frequencies of Tregs were shown. Neither monocytic myeloid-derived suppressor cells (MDSCs) nor early MDSCs changed after CIRT. TGF-β1 gene expression decreased while IL-6 showed a non-significant trend towards a decrease. Both IL-10 gene expression and plasma TGF‐β1 level were unchanged. Conclusion CIRT demonstrates the potential to elicit immune activation in localized prostate cancer patients, based on sparing lymphocytes, increased lymphocyte proliferation, enhanced T-cell functionality, together with limited induction of immunosuppressive cells and reduced expression of immunosuppressive cytokines.

Carbon Ion Radiation Therapy for Nonmetastatic Castration-Resistant Prostate Cancer: A Retrospective Analysis

“… 24 Although the reason for this outcome was not determined in this study, peripheral immune activation after CIRT may be responsible. 25 Despite differences in background and evaluation methods between the previous studies and our study, our findings indicate that CIRT could be a promising treatment option for nmCRPC. Additional studies validating our results with a longer follow-up are necessary.…”

Clinical application of high‐LET radiotherapy combined with immunotherapy in malignant tumors

“…CIRT has the potential to elicit immune activation of lymphocytes, such as T cells, NK cells, and DCs; increase lymphocyte proliferation; enhance lymphocyte functionality; limiting the induction of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs); and reduce the expression of immunosuppressive cytokines. Hu et al 21 assessed the immune response evoked by CIRT in 32 patients with localized prostate cancer, and the results showed that there were no significant differences in the frequencies of CD3 + , CD4 + , CD8 + T cells, and NK cells, whereas the CD4/CD8 ratio increased in all lymphocyte subsets except regulatory T cell (Tregs) proliferation and T cell functionality enhancement. However, we did not observe any changes in the MDSCs.…”

Combining theranostic/particle therapy with immunotherapy for the treatment of GU malignancies

“…Similar results were seen in 32 patients undergoing carbon ion therapy for prostate cancer whereby circulating CD4+ and CD8+ lymphocytes, as well as natural killer cells, were elevated after carbon ion therapy but not after proton therapy. The production of pro‐inflammatory cytokines and the proliferation of these immune cells was also increased following carbon ion therapy 28 . The influx of pro‐inflammatory immune cells often accompanies immunosuppressive cells, such as myeloid‐derived suppressor cells (MDSCs), which inhibit T cell function and enhance the proliferation and differentiation of malignant cells.…”

“…The production of pro‐inflammatory cytokines and the proliferation of these immune cells was also increased following carbon ion therapy. 28 The influx of pro‐inflammatory immune cells often accompanies immunosuppressive cells, such as myeloid‐derived suppressor cells (MDSCs), which inhibit T cell function and enhance the proliferation and differentiation of malignant cells. In murine melanoma, tumour irradiation with carbon ions decreased the number of circulating, splenic and intratumoural MDSCs when compared with photon radiation or no treatment.…”