Wei Hu1,2,3, Yulei Pei1,2,3, Renli Ning2,3,4, Ping Li2,3,5, Zhenshan Zhang1,2,3, Zhengshan Hong2,3,5, Cihang Bao2,3,5, Xiaomao Guo6,7,8, Yun Sun9,10,11, Qing Zhang12,13,14. 1. Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China. 2. Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, China. 3. Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China. 4. Department of Research and Development, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China. 5. Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, China. 6. Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, China. guoxm1800@126.com. 7. Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China. guoxm1800@126.com. 8. Department of Research and Development, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China. guoxm1800@126.com. 9. Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, China. yun.sun@sphic.org.cn. 10. Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China. yun.sun@sphic.org.cn. 11. Department of Research and Development, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China. yun.sun@sphic.org.cn. 12. Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China. qing.zhang@sphic.org.cn. 13. Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, China. qing.zhang@sphic.org.cn. 14. Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China. qing.zhang@sphic.org.cn.
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.
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.
Authors: C Belka; H Ottinger; E Kreuzfelder; M Weinmann; M Lindemann; A Lepple-Wienhues; W Budach; H Grosse-Wilde; M Bamberg Journal: Radiother Oncol Date: 1999-02 Impact factor: 6.280
Authors: Fanny Bouquet; Anupama Pal; Karsten A Pilones; Sandra Demaria; Byron Hann; Rosemary J Akhurst; Jim S Babb; Scott M Lonning; J Keith DeWyngaert; Silvia C Formenti; Mary Helen Barcellos-Hoff Journal: Clin Cancer Res Date: 2011-10-25 Impact factor: 12.531
Authors: Laura Hartmann; Philipp Schröter; Wolfram Osen; Daniel Baumann; Rienk Offringa; Mahmoud Moustafa; Rainer Will; Jürgen Debus; Stephan Brons; Stefan Rieken; Stefan B Eichmüller Journal: Sci Rep Date: 2020-12-09 Impact factor: 4.379