Microbeam Radiotherapy—A Novel Therapeutic Approach to Overcome Radioresistance and Enhance Anti-Tumour Response in Melanoma
Abstract
:1. Introduction to Melanoma
2. Melanoma and Radiation Therapy
2.1. Radioresistance of Melanoma and Conventional RT as a Treatment Strategy
2.2. Spatially Fractionated RT Including Synchrotron-Generated MRT
3. RT-Generated Immune Response
3.1. Conventional RT and Tumour Immune Response
3.2. Combination of RT and Immunotherapy; Abscopal Effects
3.3. Immune Implications of SFRT
3.4. Activation of the Immune Response Following MRT
3.4.1. The Immune Response in Irradiated Tumours
3.4.2. The Immune Response in Normal Tissues
4. Comparative Gene Expression Analysis in MRT-Irradiated Tumours
5. MRT as a Novel Strategy for Treatment of Melanoma
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer Statistics, 2020. CA Cancer J. Clin. 2020, 70, 7–30. [Google Scholar] [CrossRef]
- Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Estimating the Global Cancer Incidence and Mortality in 2018: GLOBOCAN Sources and Methods. Int. J. Cancer 2019, 144, 1941–1953. [Google Scholar] [CrossRef] [Green Version]
- Usher-Smith, J.A.; Emery, J.; Kassianos, A.P.; Walter, F.M. Risk Prediction Models for Melanoma: A Systematic Review. Cancer Epidemiol. Biomark. Prev. 2014, 23, 1450–1463. [Google Scholar] [CrossRef] [Green Version]
- Thomas, N.E.; Kricker, A.; Waxweiler, W.T.; Dillon, P.M.; Busman, K.J.; From, L.; Groben, P.A.; Armstrong, B.K.; Anton-Culver, H.; Gruber, S.B.; et al. Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas: A Population-Based Study. JAMA Dermatol. 2014, 150, 1306–1314. [Google Scholar] [CrossRef]
- Kuk, D.; Shoushtari, A.N.; Barker, C.A.; Panageas, K.S.; Munhoz, R.R.; Momtaz, P.; Ariyan, C.E.; Brady, M.S.; Coit, D.G.; Bogatch, K.; et al. Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis. Oncologist 2016, 21, 848–854. [Google Scholar] [CrossRef] [Green Version]
- Kunte, C.; Geimer, T.; Baumert, J.; Konz, B.; Volkenandt, M.; Flaig, M.; Ruzicka, T.; Berking, C.; Schmid-Wendtner, M.-H. Prognostic Factors Associated with Sentinel Lymph Node Positivity and Effect of Sentinel Status on Survival: An Analysis of 1049 Patients with Cutaneous Melanoma. Melanoma Res. 2010, 20, 330–337. [Google Scholar] [CrossRef] [PubMed]
- Shain, A.H.; Bastian, B.C. From Melanocytes to Melanomas. Nat. Rev. Cancer 2016, 16, 345–358. [Google Scholar] [CrossRef]
- Vyas, R.; Selph, J.; Gerstenblith, M.R. Cutaneous Manifestations Associated with Melanoma. Semin. Oncol. 2016, 43, 384–389. [Google Scholar] [CrossRef]
- Keung, E.Z.; Gershenwald, J.E. The Eighth Edition American Joint Committee on Cancer (AJCC) Melanoma Staging System: Implications for Melanoma Treatment and Care. Expert Rev. Anticancer Ther. 2018, 18, 775–784. [Google Scholar] [CrossRef]
- Gershenwald, J.E.; Scolyer, R.A.; Hess, K.R.; Sondak, V.K.; Long, G.V.; Ross, M.I.; Lazar, A.J.; Faries, M.B.; Kirkwood, J.M.; McArthur, G.A.; et al. Melanoma Staging: Evidence-Based Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual. CA Cancer J. Clin. 2017, 67, 472–492. [Google Scholar] [CrossRef] [Green Version]
- Hayes, A.J.; Maynard, L.; Coombes, G.; Newton-Bishop, J.; Timmons, M.; Cook, M.; Theaker, J.; Bliss, J.M.; Thomas, J.M.; UK Melanoma Study Group; et al. Wide versus Narrow Excision Margins for High-Risk, Primary Cutaneous Melanomas: Long-Term Follow-up of Survival in a Randomised Trial. Lancet Oncol. 2016, 17, 184–192. [Google Scholar] [CrossRef] [Green Version]
- Young, S.E.; Martinez, S.R.; Faries, M.B.; Essner, R.; Wanek, L.A.; Morton, D.L. Can Surgical Therapy Alone Achieve Long-Term Cure of Melanoma Metastatic to Regional Nodes? Cancer J. 2006, 12, 207–211. [Google Scholar] [CrossRef]
- Leiter, U.; Stadler, R.; Mauch, C.; Hohenberger, W.; Brockmeyer, N.; Berking, C.; Sunderkötter, C.; Kaatz, M.; Schulte, K.-W.; Lehmann, P.; et al. Complete Lymph Node Dissection versus No Dissection in Patients with Sentinel Lymph Node Biopsy Positive Melanoma (DeCOG-SLT): A Multicentre, Randomised, Phase 3 Trial. Lancet Oncol. 2016, 17, 757–767. [Google Scholar] [CrossRef]
- Takahashi, J.; Nagasawa, S. Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review. Int. J. Mol. Sci. 2020, 21, 9324. [Google Scholar] [CrossRef]
- Dewey, D.L. The Radiosensitivity of Melanoma Cells in Culture. BJR 1971, 44, 816–817. [Google Scholar] [CrossRef]
- Barranco, S.C.; Romsdahl, M.M.; Humphrey, R.M. The Radiation Response of Human Malignant Melanoma Cells Grown in Vitro. Cancer Res. 1971, 31, 830–833. [Google Scholar] [PubMed]
- Kauffmann, A.; Rosselli, F.; Lazar, V.; Winnepenninckx, V.; Mansuet-Lupo, A.; Dessen, P.; van den Oord, J.J.; Spatz, A.; Sarasin, A. High Expression of DNA Repair Pathways Is Associated with Metastasis in Melanoma Patients. Oncogene 2008, 27, 565–573. [Google Scholar] [CrossRef] [Green Version]
- Wu, L.; Hu, Z.; Huang, Y.; Yu, Y.; Liang, W.; Zheng, Q.; Huang, X.; Huang, Y.; Lu, X.; Zhao, Y. Radiation Changes the Metabolic Profiling of Melanoma Cell Line B16. PLoS ONE 2016, 11, e0162917. [Google Scholar] [CrossRef]
- Rofstad, E.K. Radiation Biology of Malignant Melanoma. Acta Radiol. Oncol. 1986, 25, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Stevens, G.; McKay, M.J. Dispelling the Myths Surrounding Radiotherapy for Treatment of Cutaneous Melanoma. Lancet Oncol. 2006, 7, 575–583. [Google Scholar] [CrossRef]
- Chavaudra, N.; Guichard, M.; Malaise, E.P. Hypoxic Fraction and Repair of Potentially Lethal Radiation Damage in Two Human Melanomas Transplanted into Nude Mice. Radiat. Res. 1981, 88, 56–68. [Google Scholar] [CrossRef] [PubMed]
- Rofstad, E.K.; Brustad, T. Tumour Growth Delay Following Single Dose Irradiation of Human Melanoma Xenografts. Correlations with Tumour Growth Parameters, Vascular Structure and Cellular Radiosensitivity. Br. J. Cancer 1985, 51, 201–210. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Matchuk, O.N.; Zamulaeva, I.A.; Kovalev, O.A.; Saenko, A.S. Radioresistance mechanisms of side population cells in mouse melanoma cell line B16. Tsitologiia 2013, 55, 553–559. [Google Scholar] [CrossRef]
- Bastiaannet, E.; Beukema, J.C.; Hoekstra, H.J. Radiation Therapy Following Lymph Node Dissection in Melanoma Patients: Treatment, Outcome and Complications. Cancer Treat. Rev. 2005, 31, 18–26. [Google Scholar] [CrossRef]
- Keenan, L.G.; O’Sullivan, S.; Glynn, A.; Higgins, M.; Flavin, A.; Brennan, S. Clinical Review of Treatment Outcomes and Patterns of Failure with Adjuvant Radiotherapy in Node-Positive Malignant Melanoma. J. Med. Imaging Radiat. Oncol. 2017, 61, 258–262. [Google Scholar] [CrossRef]
- Eddy, K.; Chen, S. Overcoming Immune Evasion in Melanoma. Int. J. Mol. Sci. 2020, 21, 8984. [Google Scholar] [CrossRef]
- Habermalz, H.J.; Fischer, J.J. Radiation Therapy of Malignant Melanoma: Experience with High Individual Treatment Doses. Cancer 1976, 38, 2258–2262. [Google Scholar] [CrossRef]
- Lugade, A.A.; Moran, J.P.; Gerber, S.A.; Rose, R.C.; Frelinger, J.G.; Lord, E.M. Local Radiation Therapy of B16 Melanoma Tumors Increases the Generation of Tumor Antigen-Specific Effector Cells That Traffic to the Tumor. J. Immunol. 2005, 174, 7516–7523. [Google Scholar] [CrossRef] [Green Version]
- Shi, W. Role for Radiation Therapy in Melanoma. Surg. Oncol. Clin. N. Am. 2015, 24, 323–335. [Google Scholar] [CrossRef]
- Mohiuddin, M.; Stevens, J.H.; Reiff, J.E.; Huq, M.S.; Suntharalingam, N. Spatially Fractionated (GRID) Radiation for Palliative Treatment of Advanced Cancer. Radiat. Oncol. Investig. 1996, 4, 41–47. [Google Scholar] [CrossRef]
- Mohiuddin, M.; Fujita, M.; Regine, W.F.; Megooni, A.S.; Ibbott, G.S.; Ahmed, M.M. High-Dose Spatially-Fractionated Radiation (GRID): A New Paradigm in the Management of Advanced Cancers. Int. J. Radiat. Oncol. Biol. Phys. 1999, 45, 721–727. [Google Scholar] [CrossRef]
- Yan, W.; Khan, M.K.; Wu, X.; Simone, C.B.; Fan, J.; Gressen, E.; Zhang, X.; Limoli, C.L.; Bahig, H.; Tubin, S.; et al. Spatially Fractionated Radiation Therapy: History, Present and the Future. Clin. Transl. Radiat. Oncol. 2019, 20, 30–38. [Google Scholar] [CrossRef] [Green Version]
- Shirato, H.; Gupta, N.K.; Jordan, T.J.; Hendry, J.H. Lack of Late Skin Necrosis in Man after High-Dose Irradiation Using Small Field Sizes: Experiences of Grid Therapy. Br. J. Radiol. 1990, 63, 871–874. [Google Scholar] [CrossRef] [PubMed]
- Wu, X.; Ahmed, M.M.; Wright, J.; Gupta, S.; Pollack, A. On Modern Technical Approaches of Three-Dimensional High-Dose Lattice Radiotherapy (LRT). Cureus 2010, 2. [Google Scholar] [CrossRef] [Green Version]
- Wu, X.; Perez, N.C.; Zheng, Y.; Li, X.; Jiang, L.; Amendola, B.E.; Xu, B.; Mayr, N.A.; Lu, J.J.; Hatoum, G.F.; et al. The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT). Radiat. Res. 2020, 194, 737–746. [Google Scholar] [CrossRef]
- Prezado, Y.; Fois, G.R. Proton-Minibeam Radiation Therapy: A Proof of Concept. Med. Phys. 2013, 40, 031712. [Google Scholar] [CrossRef] [PubMed]
- Prezado, Y.; Jouvion, G.; Guardiola, C.; Gonzalez, W.; Juchaux, M.; Bergs, J.; Nauraye, C.; Labiod, D.; De Marzi, L.; Pouzoulet, F.; et al. Tumor Control in RG2 Glioma-Bearing Rats: A Comparison Between Proton Minibeam Therapy and Standard Proton Therapy. Int. J. Radiat. Oncol. Biol. Phys. 2019, 104, 266–271. [Google Scholar] [CrossRef]
- Dilmanian, F.A.; Zhong, Z.; Bacarian, T.; Benveniste, H.; Romanelli, P.; Wang, R.; Welwart, J.; Yuasa, T.; Rosen, E.M.; Anschel, D.J. Interlaced X-Ray Microplanar Beams: A Radiosurgery Approach with Clinical Potential. Proc. Natl. Acad. Sci. USA 2006, 103, 9709–9714. [Google Scholar] [CrossRef] [Green Version]
- Prezado, Y.; Sarun, S.; Gil, S.; Deman, P.; Bouchet, A.; Le Duc, G. Increase of Lifespan for Glioma-Bearing Rats by Using Minibeam Radiation Therapy. J. Synchrotron Radiat. 2012, 19, 60–65. [Google Scholar] [CrossRef]
- Prezado, Y.; Dos Santos, M.; Gonzalez, W.; Jouvion, G.; Guardiola, C.; Heinrich, S.; Labiod, D.; Juchaux, M.; Jourdain, L.; Sebrie, C.; et al. Transfer of Minibeam Radiation Therapy into a Cost-Effective Equipment for Radiobiological Studies: A Proof of Concept. Sci. Rep. 2017, 7, 17295. [Google Scholar] [CrossRef]
- Hadsell, M.; Zhang, J.; Laganis, P.; Sprenger, F.; Shan, J.; Zhang, L.; Burk, L.; Yuan, H.; Chang, S.; Lu, J.; et al. A First Generation Compact Microbeam Radiation Therapy System Based on Carbon Nanotube X-Ray Technology. Appl. Phys. Lett. 2013, 103, 183505. [Google Scholar] [CrossRef] [Green Version]
- Fernandez-Palomo, C.; Fazzari, J.; Trappetti, V.; Smyth, L.; Janka, H.; Laissue, J.; Djonov, V. Animal Models in Microbeam Radiation Therapy: A Scoping Review. Cancers 2020, 12, 527. [Google Scholar] [CrossRef] [Green Version]
- Eling, L.; Bouchet, A.; Nemoz, C.; Djonov, V.; Balosso, J.; Laissue, J.; Bräuer-Krisch, E.; Adam, J.F.; Serduc, R. Ultra High Dose Rate Synchrotron Microbeam Radiation Therapy. Preclinical Evidence in View of a Clinical Transfer. Radiother. Oncol. 2019, 139, 56–61. [Google Scholar] [CrossRef] [PubMed]
- Bräuer-Krisch, E.; Adam, J.-F.; Alagoz, E.; Bartzsch, S.; Crosbie, J.; DeWagter, C.; Dipuglia, A.; Donzelli, M.; Doran, S.; Fournier, P.; et al. Medical Physics Aspects of the Synchrotron Radiation Therapies: Microbeam Radiation Therapy (MRT) and Synchrotron Stereotactic Radiotherapy (SSRT). Phys. Med. 2015, 31, 568–583. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marcu, L.G.; Bezak, E.; Peukert, D.D.; Wilson, P. Translational Research in FLASH Radiotherapy-From Radiobiological Mechanisms to In Vivo Results. Biomedicines 2021, 9, 181. [Google Scholar] [CrossRef]
- Montay-Gruel, P.; Acharya, M.M.; Petersson, K.; Alikhani, L.; Yakkala, C.; Allen, B.D.; Ollivier, J.; Petit, B.; Jorge, P.G.; Syage, A.R.; et al. Long-Term Neurocognitive Benefits of FLASH Radiotherapy Driven by Reduced Reactive Oxygen Species. Proc. Natl. Acad. Sci. USA 2019, 116, 10943–10951. [Google Scholar] [CrossRef] [Green Version]
- Potez, M.; Fernandez-Palomo, C.; Bouchet, A.; Trappetti, V.; Donzelli, M.; Krisch, M.; Laissue, J.; Volarevic, V.; Djonov, V. Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms. Int. J. Radiat. Oncol. Biol. Phys. 2019, 105, 1126–1136. [Google Scholar] [CrossRef] [Green Version]
- Fernandez-Palomo, C.; Trappetti, V.; Potez, M.; Pellicioli, P.; Krisch, M.; Laissue, J.; Djonov, V. Complete Remission of Mouse Melanoma after Temporally Fractionated Microbeam Radiotherapy. Cancers 2020, 12, 2656. [Google Scholar] [CrossRef] [PubMed]
- Anderson, R.E.; Warner, N.L. Ionizing radiation and the immune response. Adv. Immunol. 1976, 24, 215–335. [Google Scholar]
- McKelvey, K.J.; Hudson, A.L.; Back, M.; Eade, T.; Diakos, C.I. Radiation, Inflammation and the Immune Response in Cancer. Mamm. Genome 2018, 29, 843–865. [Google Scholar] [CrossRef] [Green Version]
- Tálas, M.; Szolgay, E.; Várterész, V.; Koczkás, G. Influence of Acute and Fractional X-Irradiation on Induction of Interferon in Vivo. Arch. Für Virusforsch. 1972, 38, 143–148. [Google Scholar] [CrossRef]
- Desai, S.; Kumar, A.; Laskar, S.; Pandey, B.N. Cytokine Profile of Conditioned Medium from Human Tumor Cell Lines after Acute and Fractionated Doses of Gamma Radiation and Its Effect on Survival of Bystander Tumor Cells. Cytokine 2013, 61, 54–62. [Google Scholar] [CrossRef]
- Valledor, A.F.; Comalada, M.; Santamaría-Babi, L.F.; Lloberas, J.; Celada, A. Macrophage Proinflammatory Activation and Deactivation: A Question of Balance. Adv. Immunol. 2010, 108, 1–20. [Google Scholar] [CrossRef]
- Haikerwal, S.J.; Hagekyriakou, J.; MacManus, M.; Martin, O.A.; Haynes, N.M. Building Immunity to Cancer with Radiation Therapy. Cancer Lett. 2015, 368, 198–208. [Google Scholar] [CrossRef]
- Fujiwara, N.; Kobayashi, K. Macrophages in Inflammation. Curr. Drug Targets Inflamm. Allergy 2005, 4, 281–286. [Google Scholar] [CrossRef]
- Holthusen, H. Involvement of the NO/Cyclic GMP Pathway in Bradykinin-Evoked Pain from Veins in Humans. Pain 1997, 69, 87–92. [Google Scholar] [CrossRef]
- Santana, M.A.; Esquivel-Guadarrama, F. Cell Biology of T Cell Activation and Differentiation. Int. Rev. Cytol. 2006, 250, 217–274. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Auh, S.L.; Wang, Y.; Burnette, B.; Wang, Y.; Meng, Y.; Beckett, M.; Sharma, R.; Chin, R.; Tu, T.; et al. Therapeutic Effects of Ablative Radiation on Local Tumor Require CD8+ T Cells: Changing Strategies for Cancer Treatment. Blood 2009, 114, 589–595. [Google Scholar] [CrossRef] [PubMed]
- Weichselbaum, R.R.; Liang, H.; Deng, L.; Fu, Y.-X. Radiotherapy and Immunotherapy: A Beneficial Liaison? Nat. Rev. Clin. Oncol. 2017, 14, 365–379. [Google Scholar] [CrossRef]
- Krysko, D.V.; Garg, A.D.; Kaczmarek, A.; Krysko, O.; Agostinis, P.; Vandenabeele, P. Immunogenic Cell Death and DAMPs in Cancer Therapy. Nat. Rev. Cancer 2012, 12, 860–875. [Google Scholar] [CrossRef]
- Ahmed, A.; Tait, S.W.G. Targeting Immunogenic Cell Death in Cancer. Mol. Oncol. 2020, 14, 2994–3006. [Google Scholar] [CrossRef] [PubMed]
- Zitvogel, L.; Kroemer, G. Subversion of Anticancer Immunosurveillance by Radiotherapy. Nat. Immunol. 2015, 16, 1005–1007. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.; Escamilla, J.; Mok, S.; David, J.; Priceman, S.; West, B.; Bollag, G.; McBride, W.; Wu, L. CSF1R Signaling Blockade Stanches Tumor-Infiltrating Myeloid Cells and Improves the Efficacy of Radiotherapy in Prostate Cancer. Cancer Res. 2013, 73, 2782–2794. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blobe, G.C.; Schiemann, W.P.; Lodish, H.F. Role of Transforming Growth Factor β in Human Disease. Available online: https://www.nejm.org/doi/10.1056/NEJM200005043421807 (accessed on 9 June 2021).
- Lumniczky, K.; Impens, N.; Armengol, G.; Candéias, S.; Georgakilas, A.G.; Hornhardt, S.; Martin, O.A.; Rödel, F.; Schaue, D. Low Dose Ionizing Radiation Effects on the Immune System. Environ. Int. 2021, 149, 106212. [Google Scholar] [CrossRef]
- Kanagavelu, S.; Gupta, S.; Wu, X.; Philip, S.; Wattenberg, M.M.; Hodge, J.W.; Couto, M.D.; Chung, K.D.; Ahmed, M.M. In Vivo Effects of Lattice Radiation Therapy on Local and Distant Lung Cancer: Potential Role of Immunomodulation. Radiat. Res. 2014, 182, 149–162. [Google Scholar] [CrossRef] [PubMed]
- Buchbinder, E.I.; Desai, A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am. J. Clin. Oncol. 2016, 39, 98–106. [Google Scholar] [CrossRef] [Green Version]
- Vanneste, B.G.L.; Van Limbergen, E.J.; Dubois, L.; Samarska, I.V.; Wieten, L.; Aarts, M.J.B.; Marcelissen, T.; De Ruysscher, D. Immunotherapy as Sensitizer for Local Radiotherapy. Oncoimmunology 2020, 9. [Google Scholar] [CrossRef]
- Rudd, C.E. CTLA-4 Co-Receptor Impacts on the Function of Treg and CD8+ T-Cell Subsets. Eur. J. Immunol. 2009, 39, 687–690. [Google Scholar] [CrossRef] [Green Version]
- Jagodinsky, J.C.; Harari, P.M.; Morris, Z.S. The Promise of Combining Radiation Therapy with Immunotherapy. Int. J. Radiat. Oncol. Biol. Phys. 2020, 108, 6–16. [Google Scholar] [CrossRef]
- Demaria, S.; Bhardwaj, N.; McBride, W.H.; Formenti, S.C. Combining Radiotherapy and Immunotherapy: A Revived Partnership. Int. J. Radiat. Oncol. Biol. Phys. 2005, 63, 655–666. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Deng, W.; Li, N.; Neri, S.; Sharma, A.; Jiang, W.; Lin, S.H. Combining Immunotherapy and Radiotherapy for Cancer Treatment: Current Challenges and Future Directions. Front. Pharmacol. 2018, 9. [Google Scholar] [CrossRef] [Green Version]
- Demaria, S.; Formenti, S.C. The Abscopal Effect 67 Years Later: From a Side Story to Center Stage. BJR 2020, 93, 20200042. [Google Scholar] [CrossRef]
- Dewan, M.Z.; Galloway, A.E.; Kawashima, N.; Dewyngaert, J.K.; Babb, J.S.; Formenti, S.C.; Demaria, S. Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect When Combined with Anti–CTLA-4 Antibody. Clin. Cancer Res. 2009, 15, 5379–5388. [Google Scholar] [CrossRef] [Green Version]
- Golden, E.B.; Demaria, S.; Schiff, P.B.; Chachoua, A.; Formenti, S.C. An Abscopal Response to Radiation and Ipilimumab in a Patient with Metastatic Non–Small Cell Lung Cancer. Cancer Immunol. Res. 2013, 1, 365–372. [Google Scholar] [CrossRef] [Green Version]
- Postow, M.A.; Callahan, M.K.; Barker, C.A.; Yamada, Y.; Yuan, J.; Kitano, S.; Mu, Z.; Rasalan, T.; Adamow, M.; Ritter, E.; et al. Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma. N. Engl. J. Med. 2012, 366, 925–931. [Google Scholar] [CrossRef] [Green Version]
- Schaue, D.; Comin-Anduix, B.; Ribas, A.; Zhang, L.; Goodglick, L.; Sayre, J.W.; Debucquoy, A.; Haustermans, K.; McBride, W.H. T-Cell Responses to Survivin in Cancer Patients Undergoing Radiation Therapy. Clin. Cancer Res. 2008, 14, 4883–4890. [Google Scholar] [CrossRef] [Green Version]
- Golden, E.B.; Chhabra, A.; Chachoua, A.; Adams, S.; Donach, M.; Fenton-Kerimian, M.; Friedman, K.; Ponzo, F.; Babb, J.S.; Goldberg, J.; et al. Local Radiotherapy and Granulocyte-Macrophage Colony-Stimulating Factor to Generate Abscopal Responses in Patients with Metastatic Solid Tumours: A Proof-of-Principle Trial. Lancet Oncol. 2015, 16, 795–803. [Google Scholar] [CrossRef]
- Vanpouille-Box, C.; Alard, A.; Aryankalayil, M.J.; Sarfraz, Y.; Diamond, J.M.; Schneider, R.J.; Inghirami, G.; Coleman, C.N.; Formenti, S.C.; Demaria, S. DNA Exonuclease Trex1 Regulates Radiotherapy-Induced Tumour Immunogenicity. Nat. Commun. 2017, 8, 15618. [Google Scholar] [CrossRef] [PubMed]
- Tubin, S.; Ashdown, M.; Jeremic, B. Time-Synchronized Immune-Guided SBRT Partial Bulky Tumor Irradiation Targeting Hypoxic Segment While Sparing the Peritumoral Immune Microenvironment. Radiat. Oncol. 2019, 14, 220. [Google Scholar] [CrossRef] [PubMed]
- Pilones, K.A.; Vanpouille-Box, C.; Demaria, S. Combination of Radiotherapy and Immune Checkpoint Inhibitors. Semin. Radiat. Oncol. 2015, 25, 28–33. [Google Scholar] [CrossRef] [PubMed]
- Jiang, L.; Li, X.; Zhang, J.; Li, W.; Dong, F.; Chen, C.; Lin, Q.; Zhang, C.; Zheng, F.; Yan, W.; et al. Combined High-Dose LATTICE Radiation Therapy and Immune Checkpoint Blockade for Advanced Bulky Tumors: The Concept and a Case Report. Front. Oncol. 2021, 10. [Google Scholar] [CrossRef]
- Savage, T.; Pandey, S.; Guha, C. Postablation Modulation after Single High-Dose Radiation Therapy Improves Tumor Control via Enhanced Immunomodulation. Clin. Cancer Res. 2020, 26, 910–921. [Google Scholar] [CrossRef]
- Klug, F.; Prakash, H.; Huber, P.E.; Seibel, T.; Bender, N.; Halama, N.; Pfirschke, C.; Voss, R.H.; Timke, C.; Umansky, L.; et al. Low-Dose Irradiation Programs Macrophage Differentiation to an INOS+/M1 Phenotype That Orchestrates Effective T Cell Immunotherapy. Cancer Cell 2013, 24, 589–602. [Google Scholar] [CrossRef] [Green Version]
- Nahum, A.E.; Movsas, B.; Horwitz, E.M.; Stobbe, C.C.; Chapman, J.D. Incorporating Clinical Measurements of Hypoxia into Tumor Local Control Modeling of Prostate Cancer: Implications for the α/β Ratio. Int. J. Radiat. Oncol. Biol. Phys. 2003, 57, 391–401. [Google Scholar] [CrossRef]
- Theelen, W.S.M.E.; Peulen, H.M.U.; Lalezari, F.; van der Noort, V.; de Vries, J.F.; Aerts, J.G.J.V.; Dumoulin, D.W.; Bahce, I.; Niemeijer, A.-L.N.; de Langen, A.J.; et al. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients with Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019, 5, 1276–1282. [Google Scholar] [CrossRef] [PubMed]
- Sprung, C.N.; Yang, Y.; Forrester, H.B.; Li, J.; Zaitseva, M.; Cann, L.; Restall, T.; Anderson, R.L.; Crosbie, J.C.; Rogers, P.A.W. Genome-Wide Transcription Responses to Synchrotron Microbeam Radiotherapy. Radiat. Res. 2012, 178, 249. [Google Scholar] [CrossRef] [PubMed]
- Bouchet, A.; Sakakini, N.; El Atifi, M.; Le Clec’h, C.; Brauer, E.; Moisan, A.; Deman, P.; Rihet, P.; Le Duc, G.; Pelletier, L. Early Gene Expression Analysis in 9L Orthotopic Tumor-Bearing Rats Identifies Immune Modulation in Molecular Response to Synchrotron Microbeam Radiation Therapy. PLoS ONE 2013, 8, e81874. [Google Scholar]
- Bouchet, A.; Sakakini, N.; El Atifi, M.; Le Clec’h, C.; Bräuer-Krisch, E.; Rogalev, L.; Laissue, J.; Rihet, P.; Le Duc, G.; Pelletier, L. Identification of AREG and PLK1 Pathway Modulation as a Potential Key of the Response of Intracranial 9L Tumor to Microbeam Radiation Therapy. Int. J. Cancer. J. Int. Cancer 2014. in print. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Crosbie, J.C.; Paiva, P.; Ibahim, M.; Stevenson, A.; Rogers, P.A.W. In Vitro Study of Genes and Molecular Pathways Differentially Regulated by Synchrotron Microbeam Radiotherapy. Rare 2014, 182, 626–639. [Google Scholar] [CrossRef]
- Smilowitz, H.M.; Blattmann, H.; Bräuer-Krisch, E.; Bravin, A.; Di Michiel, M.; Gebbers, J.O.; Hanson, A.L.; Lyubimova, N.; Slatkin, D.N.; Stepanek, J.; et al. Synergy of Gene-Mediated Immunoprophylaxis and Microbeam Radiation Therapy for Advanced Intracerebral Rat 9L Gliosarcomas. J. Neuro-Oncol. 2006, 78, 135–143. [Google Scholar] [CrossRef]
- Brönnimann, D.; Bouchet, A.; Schneider, C.; Potez, M.; Serduc, R.; Bräuer-Krisch, E.; Graber, W.; Von Gunten, S.; Laissue, J.A.; Djonov, V. Synchrotron Microbeam Irradiation Induces Neutrophil Infiltration, Thrombocyte Attachment and Selective Vascular Damage in Vivo. Sci. Rep. 2016, 6, 33601. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Griffin, R.J.; Koonce, N.A.; Dings, R.P.M.; Siegel, E.; Moros, E.G.; Bräuer-Krisch, E.; Corry, P.M. Microbeam Radiation Therapy Alters Vascular Architecture and Tumor Oxygenation and Is Enhanced by a Galectin-1 Targeted Anti-Angiogenic Peptide. Radiat. Res. 2012, 177, 804–812. [Google Scholar] [CrossRef] [Green Version]
- Bouchet, A.; Lemasson, B.; Le Duc, G.; Maisin, C.; Bräuer-Krisch, E.; Siegbahn, E.A.; Renaud, L.; Khalil, E.; Rémy, C.; Poillot, C.; et al. Preferential Effect of Synchrotron Microbeam Radiation Therapy on Intracerebral 9l Gliosarcoma Vascular Networks. Int. J. Radiat. Oncol. Biol. Phys. 2010, 78, 1503–1512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sabatasso, S.; Fernandez-Palomo, C.; Hlushchuk, R.; Fazzari, J.; Tschanz, S.; Pellicioli, P.; Krisch, M.; Laissue, J.A.; Djonov, V. Transient and Efficient Vascular Permeability Window for Adjuvant Drug Delivery Triggered by Microbeam Radiation. Cancers 2021, 13, 2103. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Swierczak, A.; Ibahim, M.; Paiva, P.; Cann, L.; Stevenson, A.W.; Crosbie, J.C.; Anderson, R.L.; Rogers, P.A.W. Synchrotron Microbeam Radiotherapy Evokes a Different Early Tumor Immunomodulatory Response to Conventional Radiotherapy in EMT6.5 Mammary Tumors. Radiother. Oncol. 2019, 133, 93–99. [Google Scholar] [CrossRef] [PubMed]
- Arlauckas, S.P.; Garren, S.B.; Garris, C.S.; Kohler, R.H.; Oh, J.; Pittet, M.J.; Weissleder, R. Arg1 Expression Defines Immunosuppressive Subsets of Tumor-Associated Macrophages. Theranostics 2018, 8, 5842–5854. [Google Scholar] [CrossRef] [PubMed]
- Jayasingam, S.D.; Citartan, M.; Thang, T.H.; Mat Zin, A.A.; Ang, K.C.; Ch’ng, E.S. Evaluating the Polarization of Tumor-Associated Macrophages into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice. Front. Oncol. 2020, 9. [Google Scholar] [CrossRef] [Green Version]
- A-Gonzalez, N.; Quintana, J.A.; García-Silva, S.; Mazariegos, M.; González de la Aleja, A.; Nicolás-Ávila, J.A.; Walter, W.; Adrover, J.M.; Crainiciuc, G.; Kuchroo, V.K.; et al. Phagocytosis Imprints Heterogeneity in Tissue-Resident Macrophages. J. Exp. Med. 2017, 214, 1281–1296. [Google Scholar] [CrossRef] [Green Version]
- Etzerodt, A.; Moestrup, S.K. CD163 and Inflammation: Biological, Diagnostic, and Therapeutic Aspects. Antioxid. Redox Signal. 2013, 18, 2352–2363. [Google Scholar] [CrossRef] [Green Version]
- Eling, L.; Bouchet, A.; Ocadiz, A.; Adam, J.-F.; Kershmiri, S.; Elleaume, H.; Krisch, M.; Verry, C.; Laissue, J.A.; Balosso, J.; et al. Unexpected Benefits of Multiport Synchrotron Microbeam Radiation Therapy for Brain Tumors. Cancers 2021, 13, 936. [Google Scholar] [CrossRef]
- Priyadarshika, R.C.U.; Crosbie, J.C.; Kumar, B.; Rogers, P.A. Biodosimetric Quantification of Short-Term Synchrotron Microbeam versus Broad-Beam Radiation Damage to Mouse Skin Using a Dermatopathological Scoring System. Br. J. Radiol. 2011, 84, 833–842. [Google Scholar] [CrossRef] [PubMed]
- Potez, M.; Bouchet, A.; Wagner, J.; Donzelli, M.; Bräuer-Krisch, E.; Hopewell, J.W.; Laissue, J.; Djonov, V. Effects of Synchrotron X-Ray Micro-Beam Irradiation on Normal Mouse Ear Pinnae. Int. J. Radiat. Oncol. Biol. Phys. 2018, 101, 680–689. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ventura, J.; Lobachevsky, P.N.; Palazzolo, J.S.; Forrester, H.; Haynes, N.M.; Ivashkevich, A.; Stevenson, A.W.; Hall, C.J.; Ntargaras, A.; Kotsaris, V.; et al. Localized Synchrotron Irradiation of Mouse Skin Induces Persistent Systemic Genotoxic and Immune Responses. Cancer Res. 2017, 77, 6389–6399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lobachevsky, P.N.; Ventura, J.; Giannakandropoulou, L.; Forrester, H.; Palazzolo, J.S.; Haynes, N.M.; Stevenson, A.W.; Hall, C.J.; Mason, J.; Martin, O.A.; et al. A Functional Immune System Is Required for the Systemic Genotoxic Effects of Localized Irradiation. Int. J. Radiat. Oncol. Biol. Phys. 2019, 103, 1184–1193. [Google Scholar] [CrossRef] [PubMed]
- Forrester, H.B.; Lobachevsky, P.N.; Stevenson, A.W.; Hall, C.J.; Martin, O.A.; Sprung, C.N. Abscopal Gene Expression in Response to Synchrotron Radiation Indicates a Role for Immunological and DNA Damage Response Genes. Radiat. Res. 2020, 194, 678–687. [Google Scholar] [CrossRef]
- Fernandez-Palomo, C.; Schültke, E.; Bräuer-Krisch, E.; Laissue, J.A.; Blattmann, H.; Seymour, C.; Mothersill, C. Investigation of Abscopal and Bystander Effects in Immunocompromised Mice after Exposure to Pencilbeam and Microbeam Synchrotron Radiation. Health Phys. 2016, 111, 149–159. [Google Scholar] [CrossRef] [Green Version]
- Durinck, S.; Spellman, P.T.; Birney, E.; Huber, W. Mapping Identifiers for the Integration of Genomic Datasets with the R/Bioconductor Package BiomaRt. Nat. Protoc. 2009, 4, 1184–1191. [Google Scholar] [CrossRef] [Green Version]
- Lin, G.; Chai, J.; Yuan, S.; Mai, C.; Cai, L.; Murphy, R.W.; Zhou, W.; Luo, J. VennPainter: A Tool for the Comparison and Identification of Candidate Genes Based on Venn Diagrams. PLoS ONE 2016, 11. [Google Scholar] [CrossRef] [Green Version]
- Tilton, S.C.; Markillie, L.M.; Hays, S.; Taylor, R.C.; Stenoien, D.L. Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue. Rare 2016, 186, 531–538. [Google Scholar] [CrossRef]
- Palomino, D.C.T.; Marti, L.C. Chemokines and Immunity. Einstein 2015, 13, 469–473. [Google Scholar] [CrossRef] [Green Version]
- Kitamura, T.; Fujishita, T.; Loetscher, P.; Revesz, L.; Hashida, H.; Kizaka-Kondoh, S.; Aoki, M.; Taketo, M.M. Inactivation of Chemokine (C-C Motif) Receptor 1 (CCR1) Suppresses Colon Cancer Liver Metastasis by Blocking Accumulation of Immature Myeloid Cells in a Mouse Model. Proc. Natl. Acad. Sci. USA 2010, 107, 13063–13068. [Google Scholar] [CrossRef] [Green Version]
- Kimura, S.H.; Ikawa, M.; Ito, A.; Okabe, M.; Nojima, H. Cyclin G1 Is Involved in G2/M Arrest in Response to DNA Damage and in Growth Control after Damage Recovery. Oncogene 2001, 20, 3290–3300. [Google Scholar] [CrossRef] [Green Version]
- Wischhusen, J.; Melero, I.; Fridman, W.H. Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front. Immunol. 2020, 11, 951. [Google Scholar] [CrossRef] [PubMed]
- Seo, J.-Y.; Yaneva, R.; Cresswell, P. Viperin: A Multifunctional, Interferon-Inducible Protein That Regulates Virus Replication. Cell Host Microbe 2011, 10, 534–539. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yan, H.H.; Jiang, J.; Pang, Y.; Achyut, B.; Lizardo, M.; Liang, X.; Hunter, K.; Khanna, C.; Hollander, C.; Yang, L. CCL9 Induced by TGF-β Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ. Cancer Res. 2015, 75, 5283–5298. [Google Scholar] [CrossRef] [Green Version]
- Ibahim, M.J.; Yang, Y.; Crosbie, J.C.; Stevenson, A.; Cann, L.; Paiva, P.; Rogers, P.A. Eosinophil-Associated Gene Pathways but Not Eosinophil Numbers Are Differentially Regulated between Synchrotron Microbeam Radiation Treatment and Synchrotron Broad-Beam Treatment by 48 Hours Postirradiation. Radiat. Res. 2015, 185, 60. [Google Scholar] [CrossRef]
- Crosbie, J.C.; Anderson, R.L.; Rothkamm, K.; Restall, C.M.; Cann, L.; Ruwanpura, S.; Meachem, S.; Yagi, N.; Svalbe, I.; Lewis, R.A.; et al. Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly from Cells in Normal Tissues. Int. J. Radiat. Oncol. Biol. Phys. 2010, 77, 886–894. [Google Scholar] [CrossRef] [PubMed]
- Potez, M.; Trappetti, V.; Bouchet, A.; Fernandez-Palomo, C.; Güç, E.; Kilarski, W.W.; Hlushchuk, R.; Laissue, J.; Djonov, V. Characterization of a B16-F10 Melanoma Model Locally Implanted into the Ear Pinnae of C57BL/6 Mice. PLoS ONE 2018, 13, e0206693. [Google Scholar] [CrossRef] [PubMed]
Tumor Model | Assay Type | MRT Effects on Tumor Immune Response | Reference |
Glioblastoma in rat | Oligonucleotide microarray | Upregulation of genes associated with inflammation, NK or CD8+ T cells | Bouchet et al., 2013 [88] |
Glioblastoma in rat | Oligonucleotide microarray | Upregulation of transcripts indicating the presence of DCs, monocytes, and macrophages | Bouchet et al., 2014 [89] |
Glioblastoma in rat | IHC | Increase of infiltrated macrophages | Eling et al., 2021 [101] |
Mammary EMT6.5 in mouse | Whole genome analysis | Upregulation of genes related to inflammation, IFN signalling, antigen presentation | Sprung et al., 2012 [87] |
Mammary EMT6.5 cell line | Whole genome analysis | Upregulation of pathways involved in inflammation and lymphocyte activation | Yang et al., 2014 [90] |
Mammary EMT6.5 in mouse | Flow cytometry, IHC | Decrease in tumour-associated macrophages and neutrophils; increase of infiltrated T cells | Yang et al., 2019 [96] |
Melanoma B16F10 in mouse | Cytokine BioPlex analysis, IHC | Increase of monocyte-attracting cytokines; Increase of infiltrated macrophages, CD4+ and CD8+ T cells, NK cells | Potez et al., 2019 [47] |
Melanoma B16F10 in mouse | IHC | Presence of melanophages at the place of tumor cells and absence of metastasis up to 18 months post-treatment | Fernandez-Palomo et al., 2020 [48] |
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Trappetti, V.; Fazzari, J.M.; Fernandez-Palomo, C.; Scheidegger, M.; Volarevic, V.; Martin, O.A.; Djonov, V.G. Microbeam Radiotherapy—A Novel Therapeutic Approach to Overcome Radioresistance and Enhance Anti-Tumour Response in Melanoma. Int. J. Mol. Sci. 2021, 22, 7755. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147755
Trappetti V, Fazzari JM, Fernandez-Palomo C, Scheidegger M, Volarevic V, Martin OA, Djonov VG. Microbeam Radiotherapy—A Novel Therapeutic Approach to Overcome Radioresistance and Enhance Anti-Tumour Response in Melanoma. International Journal of Molecular Sciences. 2021; 22(14):7755. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147755
Chicago/Turabian StyleTrappetti, Verdiana, Jennifer M. Fazzari, Cristian Fernandez-Palomo, Maximilian Scheidegger, Vladislav Volarevic, Olga A. Martin, and Valentin G. Djonov. 2021. "Microbeam Radiotherapy—A Novel Therapeutic Approach to Overcome Radioresistance and Enhance Anti-Tumour Response in Melanoma" International Journal of Molecular Sciences 22, no. 14: 7755. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147755