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Particle radiotherapy and molecular therapies: mechanisms and strategies towards clinical applications

Part of: Advancements in the radiobiology of low and high-LET radiation

Published online by Cambridge University Press:  01 February 2022

Alexander Helm ,
Claudia Fournier  and
Marco Durante Open the ORCID record for Marco Durante [Opens in a new window]
Alexander Helm
Affiliation:
Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany
Claudia Fournier
Affiliation:
Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany
Marco Durante*
Affiliation:
Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany Technische Universität Darmstadt, Institute of Condensed Matter Physics, Darmstadt, Germany
*
Author for correspondence: Marco Durante, E-mail: [email protected]
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Abstract

Immunotherapy and targeted therapy are now commonly used in clinical trials in combination with radiotherapy for several cancers. While results are promising and encouraging, the molecular mechanisms of the interaction between the drugs and radiation remain largely unknown. This is especially important when switching from conventional photon therapy to particle therapy using protons or heavier ions. Different dose deposition patterns and molecular radiobiology can in fact modify the interaction with drugs and their effectiveness. We will show here that whilst the main molecular players are the same after low and high linear energy transfer radiation exposure, significant differences are observed in post-exposure signalling pathways that may lead to different effects of the drugs. We will also emphasise that the problem of the timing between drug administration and radiation and the fractionation regime are critical issues that need to be addressed urgently to achieve optimal results in combined treatments with particle therapy.

Keywords

Carbon ionschemoradiotherapyimmunotherapyproton therapytargeted therapy
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 24 , 2022 , e8
Copyright
Copyright © GSI 2022. Published by Cambridge University Press

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References

Zhong, L et al. (2021) Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduction and Targeted Therapy 6, 201.CrossRefGoogle ScholarPubMed
Gonzales Carazas, MM, Pinto, JA and Casado, FL (2021) Biological bases of cancer immunotherapy. Expert Reviews in Molecular Medicine 23, e3.CrossRefGoogle ScholarPubMed
Durante, M, Debus, J and Loeffler, JS (2021) Physics and biomedical challenges of cancer therapy with accelerated heavy ions. Nature Reviews Physics 3, 777–790.CrossRefGoogle ScholarPubMed
Formenti, SC and Demaria, S (2009) Systemic effects of local radiotherapy. The Lancet Oncology 10, 718–726.CrossRefGoogle ScholarPubMed
Abuodeh, Y, Venkat, P and Kim, S (2016) Systematic review of case reports on the abscopal effect. Current Problems in Cancer 40, 25–37.CrossRefGoogle ScholarPubMed
Ngwa, W et al. (2018) Using immunotherapy to boost the abscopal effect. Nature Reviews Cancer 18, 313–322.CrossRefGoogle ScholarPubMed
Grassberger, C et al. (2019) Assessing the interactions between radiotherapy and antitumour immunity. Nature Reviews Clinical Oncology 16, 729–745.CrossRefGoogle ScholarPubMed
Faivre-Finn, C et al. (2021) Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC – an update from the PACIFIC trial. Journal of Thoracic Oncology 16, 860–867.CrossRefGoogle ScholarPubMed
Antonia, SJ et al. (2017) Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. New England Journal of Medicine 377, 1919–1929.CrossRefGoogle ScholarPubMed
Fizazi, K et al. (2020) Final analysis of the ipilimumab versus placebo following radiotherapy phase III trial in postdocetaxel metastatic castration-resistant prostate cancer identifies an excess of long-term survivors. European Urology 78, 822–830.CrossRefGoogle ScholarPubMed
Zhu, X et al. (2021) Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial. The Lancet Oncology 22, 1093–1102.CrossRefGoogle ScholarPubMed
Theelen, WSME et al. (2021) Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. The Lancet Respiratory Medicine 9, 467–475.CrossRefGoogle ScholarPubMed
Reardon, DA et al. (2020) Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma. JAMA Oncology 6, 1003.CrossRefGoogle ScholarPubMed
Breen, WG et al. (2020) Radiation and immunotherapy: emerging mechanisms of synergy. Journal of Thoracic Disease 12, 7011–7023.CrossRefGoogle ScholarPubMed
Formenti, SC et al. (2018) Radiotherapy induces responses of lung cancer to CTLA-4 blockade. Nature Medicine 24, 1845–1851.CrossRefGoogle ScholarPubMed
Yu, J et al. (2021) Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nature Medicine 27, 152–164.CrossRefGoogle ScholarPubMed
Hou, Y et al. (2021) Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity. Science Translational Medicine 13, eabb0130.CrossRefGoogle ScholarPubMed
Durante, M, Orecchia, R and Loeffler, JS (2017) Charged-particle therapy in cancer: clinical uses and future perspectives. Nature Reviews Clinical Oncology 14, 483–495.CrossRefGoogle ScholarPubMed
Nikjoo, H et al. (1998) Track structure in radiation biology: theory and applications. International Journal of Radiation Biology 73, 355–364.CrossRefGoogle ScholarPubMed
Douglass, M, Bezak, E and Penfold, S (2015) Development of a radiation track structure clustering algorithm for the prediction of DNA DSB yields and radiation induced cell death in Eukaryotic cells. Physics in Medicine and Biology 60, 3217–3236.CrossRefGoogle ScholarPubMed
Durante, M and Paganetti, H (2016) Nuclear physics in particle therapy: a review. Reports on Progress in Physics 79, 096702.CrossRefGoogle ScholarPubMed
DeLaney, TF (2011) Proton therapy in the clinic. IMRT, IGRT, SBRT. Basel: KARGER, pp. 465–485. https://doi.org/10.1159/000322511.CrossRefGoogle Scholar
Specht, HM et al. (2015) Paving the road for modern particle therapy – what can we learn from the experience gained with fast neutron therapy in Munich? Frontiers in Oncology 5, 1–7.CrossRefGoogle ScholarPubMed
Kamada, T et al. (2015) Carbon ion radiotherapy in Japan: an assessment of 20 years of clinical experience. The Lancet Oncology 16, e93–e100.CrossRefGoogle ScholarPubMed
Kraft, G (2000) Tumor therapy with heavy charged particles. Progress in Particle and Nuclear Physics 45, 473–544.CrossRefGoogle Scholar
Linstadt, DE, Castro, JR and Phillips, TL (1991) Neon ion radiotherapy: results of the phase I/II clinical trial. International Journal of Radiation Oncology, Biology, Physics 20, 761–769.CrossRefGoogle ScholarPubMed
Dokic, I et al. (2016) Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams. Oncotarget 7, 56676–56689.CrossRefGoogle ScholarPubMed
Limsirichaikul, S et al. (2017) 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation. Oncotarget 8, 109370–109381.Google Scholar
Oike, T et al. (2016) Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy. Scientific Reports 6, 22275.CrossRefGoogle Scholar
Bobkova, E et al. (2018) Recruitment of 53BP1 proteins for DNA repair and persistence of repair clusters differ for cell types as detected by single molecule localization microscopy. International Journal of Molecular Sciences 19, 3713.CrossRefGoogle ScholarPubMed
Asaithamby, A, Hu, B and Chen, DJ (2011) Unrepaired clustered DNA lesions induce chromosome breakage in human cells. Proceedings of the National Academy of Sciences 108, 8293–8298.CrossRefGoogle ScholarPubMed
Splinter, J et al. (2010) Biological dose estimation of UVA laser microirradiation utilizing charged particle-induced protein foci. Mutagenesis 25, 289–297.CrossRefGoogle ScholarPubMed
Ibañez, IL et al. (2009) Induction and rejoining of DNA double strand breaks assessed by H2AX phosphorylation in melanoma cells irradiated with proton and lithium beams. International Journal of Radiation Oncology, Biology, Physics 74, 1226–1235.CrossRefGoogle ScholarPubMed
Averbeck, NB et al. (2016) Efficient rejoining of DNA double-strand breaks despite increased cell-killing effectiveness following spread-out Bragg peak carbon-ion irradiation. Frontiers in Oncology 6, 1–8.CrossRefGoogle ScholarPubMed
Cornforth, MN (2021) Occam's broom and the dirty DSB: cytogenetic perspectives on cellular response to changes in track structure and ionization density. International Journal of Radiation Biology 97, 1099–1108.CrossRefGoogle ScholarPubMed
Huang, R and Zhou, P-K (2021) DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy. Signal Transduction and Targeted Therapy 6, 254.CrossRefGoogle ScholarPubMed
Pilger, D, Seymour, LW and Jackson, SP (2021) Interfaces between cellular responses to DNA damage and cancer immunotherapy. Genes & Development 35, 602–618.CrossRefGoogle ScholarPubMed
Iliakis, G, Mladenov, E and Mladenova, V (2019) Necessities in the processing of DNA double strand breaks and their effects on genomic instability and cancer. Cancers 11, 1671.CrossRefGoogle ScholarPubMed
Yajima, H et al. (2013) The complexity of DNA double strand breaks is a critical factor enhancing end-resection. DNA Repair 12, 936–946.CrossRefGoogle ScholarPubMed
Iliakis, G, Murmann, T and Soni, A (2015) Alternative end-joining repair pathways are the ultimate backup for abrogated classical non-homologous end-joining and homologous recombination repair: implications for the formation of chromosome translocations. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 793, 166–175.CrossRefGoogle ScholarPubMed
Shibata, A and Jeggo, PA (2020) Canonical DNA non-homologous end-joining; capacity versus fidelity. The British Journal of Radiology 93, 20190966.CrossRefGoogle ScholarPubMed
Sallmyr, A and Tomkinson, AE (2018) Repair of DNA double-strand breaks by mammalian alternative end-joining pathways. Journal of Biological Chemistry 293, 10536–10546.CrossRefGoogle ScholarPubMed
Zhang, Y and Jasin, M (2011) An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway. Nature Structural & Molecular Biology 18, 80–84.CrossRefGoogle ScholarPubMed
Lee-Theilen, M et al. (2010) CtIP promotes microhomology-mediated alternative end joining during class-switch recombination. Nature Structural & Molecular Biology 18, 75–79.CrossRefGoogle ScholarPubMed
Averbeck, NB et al. (2014) DNA end resection is needed for the repair of complex lesions in G1-phase human cells. Cell Cycle 13, 2509–2516.CrossRefGoogle ScholarPubMed
Jeggo, PA, Geuting, V and Löbrich, M (2011) The role of homologous recombination in radiation-induced double-strand break repair. Radiotherapy and Oncology 101, 7–12.CrossRefGoogle ScholarPubMed
Nickoloff, JA, Sharma, N and Taylor, L (2020) Clustered DNA double-strand breaks: biological effects and relevance to cancer radiotherapy. Genes 11, 99.CrossRefGoogle ScholarPubMed
van de Kamp, G et al. (2021) DNA double strand break repair pathways in response to different types of ionizing radiation. Frontiers in Genetics 12, 1–16. doi: https://doi.org/10.3389/fgene.2021.738230.CrossRefGoogle ScholarPubMed
Fontana, AO et al. (2015) Differential DNA repair pathway choice in cancer cells after proton- and photon-irradiation. Radiotherapy and Oncology 116, 374–380.CrossRefGoogle ScholarPubMed
Grosse, N et al. (2014) Deficiency in homologous recombination renders mammalian cells more sensitive to proton versus photon irradiation. International Journal of Radiation Oncology Biology Physics 88, 175–181.CrossRefGoogle ScholarPubMed
Deycmar, S et al. (2020) The relative biological effectiveness of proton irradiation in dependence of DNA damage repair. The British Journal of Radiology 93, 20190494.CrossRefGoogle ScholarPubMed
Gerelchuluun, A et al. (2015) The major DNA repair pathway after both proton and carbon-ion radiation is NHEJ, but the HR pathway is more relevant in carbon ions. Radiation Research 183, 345356.CrossRefGoogle ScholarPubMed
Soni, A et al. (2020) Chromosome breaks generated by low doses of ionizing radiation in G2-phase are processed exclusively by gene conversion. DNA Repair 89, 102828.CrossRefGoogle ScholarPubMed
Dias, MP et al. (2021) Understanding and overcoming resistance to PARP inhibitors in cancer therapy. Nature Reviews Clinical Oncology 18, 773–791. doi: https://doi.org/10.1038/s41571-021-00532-x.CrossRefGoogle ScholarPubMed
Curtin, NJ (2005) PARP inhibitors for cancer therapy. Expert Reviews in Molecular Medicine 7, 1–20.CrossRefGoogle ScholarPubMed
Takahashi, A et al. (2014) Nonhomologous end-joining repair plays a more important role than homologous recombination repair in defining radiosensitivity after exposure to high-LET radiation. Radiation Research 182, 338–344.CrossRefGoogle Scholar
Ma, H et al. (2015) Combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kills cancer cells. Radiation Oncology 10, 225.CrossRefGoogle ScholarPubMed
Liu, X et al. (2018) Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways. Radiotherapy and Oncology 129, 84–94.CrossRefGoogle ScholarPubMed
Zhou, Q et al. (2021) Inhibition of ATM induces hypersensitivity to proton irradiation by upregulating toxic end joining. Cancer Research 81, 3333–3346.CrossRefGoogle ScholarPubMed
Christmann, M and Kaina, B (2019) Epigenetic regulation of DNA repair genes and implications for tumor therapy. Mutation Research/Reviews in Mutation Research 780, 15–28.CrossRefGoogle ScholarPubMed
Fernandez, A et al. (2021) Epigenetic mechanisms in DNA double strand break repair: a clinical review. Frontiers in Molecular Biosciences 8, 1–20. doi: https://doi.org/10.3389/fmolb.2021.685440.CrossRefGoogle ScholarPubMed
Goetz, W, Morgan, MNM and Baulch, JE (2011) The effect of radiation quality on genomic DNA methylation profiles in irradiated human cell lines. Radiation Research 175, 575–587.CrossRefGoogle ScholarPubMed
Aypar, U, Morgan, WF and Baulch, JE (2011) Radiation-induced epigenetic alterations after low and high LET irradiations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 707, 24–33.CrossRefGoogle ScholarPubMed
Miousse, IR, Kutanzi, KR and Koturbash, I (2017) Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications. International Journal of Radiation Biology 93, 457–469.CrossRefGoogle ScholarPubMed
Carter, RJ et al. (2018) Complex DNA damage induced by high linear energy transfer alpha-particles and protons triggers a specific cellular DNA damage response. International Journal of Radiation Oncology Biology Physics 100, 776–784.CrossRefGoogle ScholarPubMed
Nickson, CM et al. (2021) USP9X is required to maintain cell survival in response to high-LET radiation. Frontiers in Oncology 11, 1–12. doi: https://doi.org/10.3389/fonc.2021.671431.CrossRefGoogle ScholarPubMed
Himmels, S-F and Sartori, AA (2016) Controlling DNA-end resection: an emerging task for ubiquitin and SUMO. Frontiers in Genetics 7, 1–7. doi: https://doi.org/10.3389/fgene.2016.00152.CrossRefGoogle ScholarPubMed
Schmidt, CK et al. (2015) Systematic E2 screening reveals a UBE2D–RNF138–CtIP axis promoting DNA repair. Nature Cell Biology 17, 1458–1470.CrossRefGoogle ScholarPubMed
Grundy, GJ and Parsons, JL (2020) Base excision repair and its implications to cancer therapy. Essays in Biochemistry 64, 831–843.Google ScholarPubMed
Hughes, JR and Parsons, JL (2020) The E3 ubiquitin ligase NEDD4L targets OGG1 for ubiquitylation and modulates the cellular DNA damage response. Frontiers in Cell and Developmental Biology 8, 1–13. doi: https://doi.org/10.3389/fcell.2020.607060.CrossRefGoogle ScholarPubMed
Jakob, B et al. (2009) Live cell microscopy analysis of radiation-induced DNA double-strand break motion. Proceedings of the National Academy of Sciences of the USA 106, 3172–3177.CrossRefGoogle ScholarPubMed
Kochan, JA et al. (2019) Ultra-soft X-ray system for imaging the early cellular responses to X-ray induced DNA damage. Nucleic Acids Research 47, e100.CrossRefGoogle ScholarPubMed
Jakob, B et al. (2020) Differential repair protein recruitment at sites of clustered and isolated DNA double-strand breaks produced by high-energy heavy ions. Scientific Reports 10, 1443.CrossRefGoogle ScholarPubMed
Averbeck, NB and Durante, M (2011) Protein acetylation within the cellular response to radiation. Journal of Cellular Physiology 226, 962–967.CrossRefGoogle ScholarPubMed
Choi, C et al. (2021) Downregulation of Mcl-1 by panobinostat potentiates proton beam therapy in hepatocellular carcinoma cells. Cells 10, 554.CrossRefGoogle ScholarPubMed
Ferrari, B et al. (2021) A new platinum-based prodrug candidate for chemotherapy and its synergistic effect with hadrontherapy: novel strategy to treat glioblastoma. Frontiers in Neuroscience 15, 1–28. doi: https://doi.org/10.3389/fnins.2021.589906.CrossRefGoogle ScholarPubMed
Selzer, E and Kornek, G (2013) Targeted drugs in combination with radiotherapy for the treatment of solid tumors: current state and future developments. Expert Review of Clinical Pharmacology 6, 663–676.CrossRefGoogle ScholarPubMed
Wilson, G, Bentzen, S and Harari, P (2006) Biologic basis for combining drugs with radiation. Seminars in Radiation Oncology 16, 2–9.CrossRefGoogle Scholar
Konings, K et al. (2020) Combination therapy with charged particles and molecular targeting: a promising avenue to overcome radioresistance. Frontiers in Oncology 10, 1–21. doi: https://doi.org/10.3389/fonc.2020.00128.CrossRefGoogle ScholarPubMed
Scifoni, E et al. (2013) Including oxygen enhancement ratio in ion beam treatment planning: model implementation and experimental verification. Physics in Medicine and Biology 58, 3871–3895.CrossRefGoogle ScholarPubMed
Mori, E et al. (2009) High LET heavy ion radiation induces p53-independent apoptosis. Journal of Radiation Research 50, 37–42.CrossRefGoogle ScholarPubMed
Maalouf, M et al. (2009) Different mechanisms of cell death in radiosensitive and radioresistant P53 mutated head and neck squamous cell carcinoma cell lines exposed to carbon ions and X-rays. International Journal of Radiation Oncology Biology Physics 74, 200–209.CrossRefGoogle ScholarPubMed
Durante, M, Brenner, DJ and Formenti, SC (2016) Does heavy ion therapy work through the immune system? International Journal of Radiation Oncology, Biology, Physics 96, 934–936.CrossRefGoogle ScholarPubMed
Van Limbergen, EJ et al. (2017) Combining radiotherapy with immunotherapy: the past, the present and the future. The British Journal of Radiology 90, 20170157.CrossRefGoogle ScholarPubMed
Durante, M and Formenti, S (2020) Harnessing radiation to improve immunotherapy: better with particles? The British Journal of Radiology 93, 20190224.CrossRefGoogle ScholarPubMed
Lambin, P et al. (2020) Lymphocyte-sparing radiotherapy: the rationale for protecting lymphocyte-rich organs when combining radiotherapy with immunotherapy. Seminars in Radiation Oncology 30, 187–193.CrossRefGoogle ScholarPubMed
Davuluri, R et al. (2017) Lymphocyte nadir and esophageal cancer survival outcomes after chemoradiation therapy. International Journal of Radiation Oncology, Biology, Physics 99, 128–135.CrossRefGoogle ScholarPubMed
Durante, M et al. (2000) X-rays vs. carbon-ion tumor therapy: cytogenetic damage in lymphocytes. International Journal of Radiation Oncology, Biology, Physics 47, 793–798.CrossRefGoogle ScholarPubMed
Mohan, R et al. (2020) Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons. Neuro-Oncology 23, 284–294. doi: https://doi.org/10.1093/neuonc/noaa182.CrossRefGoogle Scholar
Kim, N et al. (2021) Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer: a comparative analysis of proton versus photon therapy. Radiotherapy and Oncology 156, 166–173.CrossRefGoogle ScholarPubMed
De, B et al. (2021) Radiation-associated lymphopenia and outcomes of patients with unresectable hepatocellular carcinoma treated with radiotherapy. Journal of Hepatocellular Carcinoma 8, 57–69.CrossRefGoogle ScholarPubMed
Venkatesulu, BP et al. (2018) A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors. Critical Reviews in Oncology/Hematology 123, 42–51.CrossRefGoogle ScholarPubMed
Chen, D et al. (2020) Interaction between lymphopenia, radiotherapy technique, dosimetry, and survival outcomes in lung cancer patients receiving combined immunotherapy and radiotherapy. Radiotherapy and Oncology 150, 114–120.CrossRefGoogle ScholarPubMed
Fransen, MF et al. (2018) Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy. JCI Insight 3, 1–7.CrossRefGoogle ScholarPubMed
Marciscano, AE et al. (2018) Elective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapy. Clinical Cancer Research 24, 5058–5071.CrossRefGoogle ScholarPubMed
Walshaw, RC, Honeychurch, J and Illidge, TM (2016) Stereotactic ablative radiotherapy and immunotherapy combinations: turning the future into systemic therapy? The British Journal of Radiology 89, 20160472.CrossRefGoogle ScholarPubMed
Demaria, S and Formenti, SC (2012) Radiation as an immunological adjuvant: current evidence on dose and fractionation. Frontiers in Oncology 2, 1–7.CrossRefGoogle ScholarPubMed
Formenti, SC (2017) Optimizing dose per fraction: a new chapter in the story of the abscopal effect? International Journal of Radiation Oncology, Biology, Physics 99, 677–679.CrossRefGoogle ScholarPubMed
Dewan, MZ et al. (2009) Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clinical Cancer Research 15, 5379–5388.CrossRefGoogle Scholar
Schaue, D et al. (2012) Maximizing tumor immunity with fractionated radiation. International Journal of Radiation Oncology, Biology, Physics 83, 1306–1310.CrossRefGoogle ScholarPubMed
Reijmen, E et al. (2021) Fractionated radiation severely reduces the number of CD8+ T cells and mature antigen presenting cells within lung tumors. International Journal of Radiation Oncology, Biology, Physics 111, 272–283.CrossRefGoogle ScholarPubMed
Sia, J et al. (2021) Regulatory T cells shape the differential impact of radiation dose-fractionation schedules on host innate and adaptive antitumor immune defenses. International Journal of Radiation Oncology, Biology, Physics 111, 502–514.CrossRefGoogle ScholarPubMed
Barsoumian, HB et al. (2020) Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma. Journal for ImmunoTherapy of Cancer 8, e000537.CrossRefGoogle ScholarPubMed
Herrera, FG et al. (2021) Low dose radiotherapy reverses tumor immune desertification and resistance to immunotherapy. Cancer Discovery 12, 108–133. doi: https://doi.org/10.1158/2159-8290.CD-21-0003.CrossRefGoogle ScholarPubMed
Chabanon, RM et al. (2021) Targeting the DNA damage response in immuno-oncology: developments and opportunities. Nature Reviews Cancer 21, 701–717. doi: https://doi.org/10.1038/s41568-021-00386-6.CrossRefGoogle ScholarPubMed
Uchihara, Y et al. (2021) Modulation of immune responses by DNA damage signaling. DNA Repair 104, 103135.CrossRefGoogle ScholarPubMed
Sato, H et al. (2017) DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nature Communications 8, 1–11. doi: https://doi.org/10.1038/s41467-017-01883-9.CrossRefGoogle ScholarPubMed
Wang, W et al. (2019) Upregulation of PD-L1 via HMGB1-activated IRF3 and NF-κB contributes to UV radiation-induced immune suppression. Cancer Research 79, 2909–2922. doi: https://doi.org/10.1158/0008-5472.CAN-18-3134.CrossRefGoogle ScholarPubMed
Iijima, M et al. (2020) Significance of PD-L1 expression in carbon-ion radiotherapy for uterine cervical adeno/adenosquamous carcinoma. Journal of Gynecologic Oncology 31, 1–14. doi: https://doi.org/10.3802/jgo.2020.31.e19.CrossRefGoogle ScholarPubMed
Roobol, SJ et al. (2020) Comparison of high- and low-LET radiation-induced DNA double-strand break processing in living cells. International Journal of Molecular Sciences 21, 6602.CrossRefGoogle ScholarPubMed
Shevtsov, M et al. (2019) Novel approaches to improve the efficacy of immuno-radiotherapy. Frontiers in Oncology 9, 1–16. doi: https://doi.org/10.3389/fonc.2019.00156.CrossRefGoogle ScholarPubMed
Petroni, G et al. (2020) Immunomodulation by anticancer cell cycle inhibitors. Nature Reviews Immunology 20, 669–679.CrossRefGoogle ScholarPubMed
Hashizume, R et al. (2016) Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth. Neuro-Oncology 18, 1519–1528.Google ScholarPubMed
Fernández-Aroca, DM et al. (2019) P53 pathway is a major determinant in the radiosensitizing effect of palbociclib: implication in cancer therapy. Cancer Letters 451, 23–33.CrossRefGoogle ScholarPubMed
Petroni, G et al. (2021) Radiotherapy delivered before CDK4/6 inhibitors mediates superior therapeutic effects in ER+breast cancer. Clinical Cancer Research 27, 1855–1863.CrossRefGoogle ScholarPubMed
Galluzzi, L et al. (2020) Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. Journal for ImmunoTherapy of Cancer 8, 1–22.CrossRefGoogle ScholarPubMed
Golden, EB et al. (2014) Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. OncoImmunology 3, 1–13. doi: https://doi.org/10.4161/onci.28518.CrossRefGoogle ScholarPubMed
Gameiro, SR et al. (2016) Tumor cells surviving exposure to proton or photon radiation share a common immunogenic modulation signature, rendering them more sensitive to T cell-mediated killing. International Journal of Radiation Oncology, Biology, Physics 95, 120–130.CrossRefGoogle ScholarPubMed
Huang, Y et al. (2019) Comparison of the effects of photon, proton and carbon-ion radiation on the ecto-calreticulin exposure in various tumor cell lines. Annals of Translational Medicine 7, 542–542.CrossRefGoogle ScholarPubMed
Ando, K et al. (2017) Intravenous dendritic cell administration enhances suppression of lung metastasis induced by carbon-ion irradiation. Journal of Radiation Research 58, 446–455.CrossRefGoogle ScholarPubMed
Yoshimoto, Y et al. (2015) Carbon-ion beams induce production of an immune mediator protein, high mobility group box 1, at levels comparable with X-ray irradiation. Journal of Radiation Research 56, 509–514.CrossRefGoogle ScholarPubMed
Onishi, M et al. (2018) High linear energy transfer carbon-ion irradiation increases the release of the immune mediator high mobility group box 1 from human cancer cells. Journal of Radiation Research 59, 541–546.CrossRefGoogle ScholarPubMed
Takahashi, Y et al. (2019) Carbon ion irradiation enhances the antitumor efficacy of dual immune checkpoint blockade therapy both for local and distant sites in murine osteosarcoma. Oncotarget 10, 633–646.CrossRefGoogle ScholarPubMed
Rizvi, NA et al. (2015) Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128.CrossRefGoogle ScholarPubMed
Lhuillier, C et al. (2019) Radiation therapy and anti-tumor immunity: exposing immunogenic mutations to the immune system. Genome Medicine 11, 40.CrossRefGoogle ScholarPubMed
Lussier, DM et al. (2021) Radiation-induced neoantigens broaden the immunotherapeutic window of cancers with low mutational loads. Proceedings of the National Academy of Sciences 118, e2102611118.CrossRefGoogle ScholarPubMed
Kiefer, J (2002) Mutagenic effects of heavy charged particles. Journal of Radiation Research 43, S21–S25.CrossRefGoogle ScholarPubMed
Ritter, S and Durante, M (2010) Heavy-ion induced chromosomal aberrations: a review. Mutation Research – Genetic Toxicology and Environmental Mutagenesis 701, 38–46.CrossRefGoogle ScholarPubMed
Rose Li, Y et al. (2020) Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice. Nature Communications 11, 394.CrossRefGoogle ScholarPubMed
Jiang, M et al. (2020) cGAS-STING, an important pathway in cancer immunotherapy. Journal of Hematology & Oncology 13, 81.CrossRefGoogle ScholarPubMed
Chen, Q, Sun, L and Chen, ZJ (2016) Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing. Nature Immunology 17, 1142–1149.CrossRefGoogle ScholarPubMed
Bakhoum, SF et al. (2018) Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 553, 467–472.CrossRefGoogle ScholarPubMed
Hopfner, K-P and Hornung, V (2020) Molecular mechanisms and cellular functions of cGAS–STING signalling. Nature Reviews Molecular Cell Biology 21, 501–521.CrossRefGoogle ScholarPubMed
Vanpouille-Box, C et al. (2017) DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nature Communications 8, 15618.CrossRefGoogle ScholarPubMed
Vanpouille-Box, C, Formenti, SC and Demaria, S (2017) TREX1 dictates the immune fate of irradiated cancer cells. OncoImmunology 6, e1339857.CrossRefGoogle ScholarPubMed
Pang, D et al. (2016) Short DNA fragments are a hallmark of heavy charged-particle irradiation and may underlie their greater therapeutic efficacy. Frontiers in Oncology 6, 130.CrossRefGoogle ScholarPubMed
Durante, M and Formenti, SC (2018) Radiation-induced chromosomal aberrations and immunotherapy: micronuclei, cytosolic DNA, and interferon-production pathway. Frontiers in Oncology 8, 1–9. doi: https://doi.org/10.3389/fonc.2018.00192.CrossRefGoogle ScholarPubMed
Harding, SM et al. (2017) Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548, 466–470.CrossRefGoogle ScholarPubMed
Ungricht, R and Kutay, U (2017) Mechanisms and functions of nuclear envelope remodelling. Nature Reviews Molecular Cell Biology 18, 229–245.CrossRefGoogle ScholarPubMed
Ebner, DK et al. (2017) Generating and grading the abscopal effect: proposal for comprehensive evaluation of combination immunoradiotherapy in mouse models. Translational Cancer Research 6, S892–S899.CrossRefGoogle Scholar
Ohkubo, Y et al. (2010) Combining carbon ion radiotherapy and local injection of α-galactosylceramide-pulsed dendritic cells inhibits lung metastases in an in vivo murine model. International Journal of Radiation Oncology, Biology, Physics 78, 1524–1531.CrossRefGoogle Scholar
Shimokawa, T et al. (2016) The future of combining carbon-ion radiotherapy with immunotherapy: evidence and progress in mouse models. International Journal of Particle Therapy 3, 61–70.CrossRefGoogle ScholarPubMed
Matsunaga, A et al. (2010) Carbon-ion beam treatment induces systemic antitumor immunity against murine squamous cell carcinoma. Cancer 116, 3740–3748.CrossRefGoogle ScholarPubMed
Helm, A et al. (2021) Reduction of lung metastases in a mouse osteosarcoma model treated with carbon ions and immune checkpoint inhibitors. International Journal of Radiation Oncology, Biology, Physics 109, 594–602.CrossRefGoogle Scholar
Wei, J et al. (2021) Sequence of αPD-1 relative to local tumor irradiation determines the induction of abscopal antitumor immune responses. Science Immunology 6, eabg0117.CrossRefGoogle ScholarPubMed
Moore, C et al. (2021) Personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) in preclinical models enhances single-agent immune checkpoint blockade. International Journal of Radiation Oncology, Biology, Physics 110, 1306–1316.CrossRefGoogle ScholarPubMed
Morris, Z et al. (2021) Future directions in the use of SAbR for the treatment of oligometastatic cancers. Seminars in Radiation Oncology 31, 253–262.CrossRefGoogle ScholarPubMed
He, K et al. (2021) Pulsed radiation therapy to improve systemic control of metastatic cancer. Frontiers in Oncology 11, 1–9. doi: https://doi.org/10.3389/fonc.2021.737425.Google ScholarPubMed
Brooks, ED and Chang, JY (2019) Time to abandon single-site irradiation for inducing abscopal effects. Nature Reviews Clinical Oncology 16, 123–135.CrossRefGoogle ScholarPubMed
Anderle, K et al. (2017) Treatment planning with intensity modulated particle therapy for multiple targets in stage {IV} non-small cell lung cancer. Physics in Medicine and Biology 63, 1–11. doi: https://doi.org/10.1088/1361-6560/aa9c62.Google Scholar
Friedrich, T, Henthorn, N and Durante, M (2021) Modeling radioimmune response – current status and perspectives. Frontiers in Oncology 11, 1–11. doi: https://doi.org/10.3389/fonc.2021.647272.CrossRefGoogle Scholar
Tinganelli, W and Durante, M (2020) Carbon ion radiobiology. Cancers 12, 3022.CrossRefGoogle ScholarPubMed
Baumann, M et al. (2016) Radiation oncology in the era of precision medicine. Nature Reviews Cancer 16, 234–249.CrossRefGoogle ScholarPubMed
Baumann, BC et al. (2020) Comparative effectiveness of proton vs photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer. JAMA Oncology 6, 237.CrossRefGoogle ScholarPubMed
Durante, M et al. (2019) Applied nuclear physics at the new high-energy particle accelerator facilities. Physics Reports 800, 1–37.CrossRefGoogle Scholar