Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

被引:3
作者
Lindner, Diana [1 ,2 ]
Arndt, Claudia [1 ]
Loureiro, Liliana Rodrigues [1 ]
Feldmann, Anja [1 ]
Kegler, Alexandra [1 ]
Koristka, Stefanie [1 ]
Berndt, Nicole [1 ]
Mitwasi, Nicola [1 ]
Bergmann, Ralf [1 ,3 ]
Frenz, Marcus [4 ]
Bachmann, Michael P. [1 ,5 ,6 ,7 ]
机构
[1] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, D-01328 Dresden, Germany
[2] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Univ Canc Ctr UCC, Tumor Immunol, D-01307 Dresden, Germany
[3] Semmelweis Univ, Inst Biophys & Radiat Biol, H-1094 Budapest, Hungary
[4] Provadis Sch Int Management & Technol AG, Fac Informat & Wirtschaftsinformat, D-65926 Frankfurt, Germany
[5] Natl Ctr Tumor Dis NCT, Partner Site Dresden, D-01307 Dresden, Germany
[6] German Canc Consortium DKTK, Partner Site Dresden, D-69120 Heidelberg, Germany
[7] German Canc Res Ctr, D-69120 Heidelberg, Germany
关键词
prostate stem cell antigen; prostate cancer; radiation; immunotherapy; bispecific T cell engager; EFFECTOR-CELLS; ANTIBODY; ANTIGEN; THERAPY; LYMPHOCYTES; CD4(+); CD8(+); TUMORS;
D O I
10.3390/ijms23147922
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-gamma and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells.
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页数:16
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共 55 条
[31]   Validation of CD98hc as a Therapeutic Target for a Combination of Radiation and Immunotherapies in Head and Neck Squamous Cell Carcinoma [J].
Koeseer, Ayse Sedef ;
Loureiro, Liliana R. ;
Jureczek, Justyna ;
Mitwasi, Nicola ;
Soto, Karla Elizabeth Gonzalez ;
Aepler, Julia ;
Bartsch, Tabea ;
Feldmann, Anja ;
Kunz-Schughart, Leoni A. ;
Linge, Annett ;
Krause, Mechthild ;
Bachmann, Michael ;
Arndt, Claudia ;
Dubrovska, Anna .
CANCERS, 2022, 14 (07)
[32]   Retargeting of regulatory T cells to surface-inducible autoantigen La/SS-B [J].
Koristka, Stefanie ;
Cartellieri, Marc ;
Arndt, Claudia ;
Bippes, Claudia C. ;
Feldmann, Anja ;
Michalk, Irene ;
Wiefel, Kristin ;
Stamova, Slava ;
Schmitz, Marc ;
Ehninger, Gerhard ;
Bornhaeuser, Martin ;
Bachmann, Michael .
JOURNAL OF AUTOIMMUNITY, 2013, 42 :105-116
[33]   Retargeting of Human Regulatory T Cells by Single-Chain Bispecific Antibodies [J].
Koristka, Stefanie ;
Cartellieri, Marc ;
Theil, Anke ;
Feldmann, Anja ;
Arndt, Claudia ;
Stamova, Slava ;
Michalk, Irene ;
Toepfer, Katrin ;
Temme, Achim ;
Kretschmer, Karsten ;
Bornhaeuser, Martin ;
Ehninger, Gerhard ;
Schmitz, Marc ;
Bachmann, Michael .
JOURNAL OF IMMUNOLOGY, 2012, 188 (03) :1551-1558
[34]   Cancer stem cell related markers of radioresistance in head and neck squamous cell carcinoma [J].
Kurth, Ina ;
Hein, Linda ;
Maebert, Katrin ;
Peitzsch, Claudia ;
Koi, Lydia ;
Cojoc, Monica ;
Kunz-Schughart, Leoni ;
Baumann, Michael ;
Dubrovska, Anna .
ONCOTARGET, 2015, 6 (33) :34494-34509
[35]   Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial [J].
Kwon, Eugene D. ;
Drake, Charles G. ;
Scher, Howard I. ;
Fizazi, Karim ;
Bossi, Alberto ;
van den Eertwegh, Alfons J. M. ;
Krainer, Michael ;
Houede, Nadine ;
Santos, Ricardo ;
Mahammedi, Hakim ;
Siobhan Ng ;
Maio, Michele ;
Franke, Fabio A. ;
Sundar, Santhanam ;
Agarwal, Neeraj ;
Bergman, Andries M. ;
Ciuleanu, Tudor E. ;
Korbenfeld, Ernesto ;
Sengelov, Lisa ;
Hansen, Steinbjorn ;
Logothetis, Christopher ;
Beer, Tomasz M. ;
McHenry, M. Brent ;
Gagnier, Paul ;
Liu, David ;
Gerritsen, Winald R. .
LANCET ONCOLOGY, 2014, 15 (07) :700-712
[36]   PD-1 Blockade in Tumors with Mismatch-Repair Deficiency [J].
Le, D. T. ;
Uram, J. N. ;
Wang, H. ;
Bartlett, B. R. ;
Kemberling, H. ;
Eyring, A. D. ;
Skora, A. D. ;
Luber, B. S. ;
Azad, N. S. ;
Laheru, D. ;
Biedrzycki, B. ;
Donehower, R. C. ;
Zaheer, A. ;
Fisher, G. A. ;
Crocenzi, T. S. ;
Lee, J. J. ;
Duffy, S. M. ;
Goldberg, R. M. ;
de la Chapelle, A. ;
Koshiji, M. ;
Bhaijee, F. ;
Huebner, T. ;
Hruban, R. H. ;
Wood, L. D. ;
Cuka, N. ;
Pardoll, D. M. ;
Papadopoulos, N. ;
Kinzler, K. W. ;
Zhou, S. ;
Cornish, T. C. ;
Taube, J. M. ;
Anders, R. A. ;
Eshleman, J. R. ;
Vogelstein, B. ;
Diaz, L. A., Jr. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) :2509-2520
[37]   Tisagenlecleucel, an approved anti-CD19 chimeric antigen receptor T-cell therapy for the treatment of leukemia [J].
Liu, Y. ;
Chen, X. ;
Han, W. ;
Zhang, Y. .
DRUGS OF TODAY, 2017, 53 (11) :597-608
[38]   Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization [J].
Maier, Patrick ;
Hartmann, Linda ;
Wenz, Frederik ;
Herskind, Carsten .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (01)
[39]   CD19-negative relapse of pediatric B-cell precursor acute lymphoblastic leukemia following blinatumomab treatment [J].
Mejstrikova, E. ;
Hrusak, O. ;
Borowitz, M. J. ;
Whitlock, J. A. ;
Brethon, B. ;
Trippett, T. M. ;
Zugmaier, G. ;
Gore, L. ;
von Stackelberg, A. ;
Locatelli, F. .
BLOOD CANCER JOURNAL, 2017, 7
[40]   Overcoming Immune Resistance With Radiation Therapy in Prostate Cancer [J].
Mulvey, Arthur ;
Muggeo-Bertin, Emilien ;
Berthold, Dominik R. ;
Herrera, Fernanda G. .
FRONTIERS IN IMMUNOLOGY, 2022, 13