Skip to main content
SpringerLink
Log in

Optimizing Radiotherapy with Immunotherapeutic Approaches

  • Chapter
  • First Online:
Immunotherapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 995))

  • 4208 Accesses

Abstract

Several factors must be considered to successfully integrate immunotherapy with radiation into clinical practice. One such factor is that concepts arising from preclinical work must be tested in combination with radiation in preclinical models to better understand how combination therapy will work in patients; examples include checkpoint inhibitors, tumor growth factor-beta (TGF-β) inhibitors, and natural killer (NK) cell therapy. Also, many radiation fields and fractionation schedules typically used in radiation therapy had been standardized before the introduction of advanced techniques for radiation planning and delivery that account for changes in tumor size, location, and motion during treatment, as well as uncertainties introduced by variations in patient setup between treatment fractions. As a result, radiation therapy may involve the use of large treatment volumes, often encompassing nodal regions that may not be irradiated with more conformal techniques. Traditional forms of radiation in particular pose challenges for combination trials with immunotherapy. This chapter explores these issues in more detail and provides insights as to how radiation therapy can be optimized to combine with immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010;303:1070–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Demaria S, Ng B, Devitt ML, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004;58:862–70.

    Article  PubMed  Google Scholar 

  3. Santarpia M, Gonzalez-Cao M, Viteri S, Karachaliou N, Altavilla G, Rosell R. Programmed cell death protein-1/programmed cell death ligand-1 pathway inhibition and predictive biomarkers: understanding transforming growth factor-beta role. Transl Lung Cancer Res. 2015;4:728–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322:271–5.

    Article  CAS  PubMed  Google Scholar 

  5. Qureshi OS, Zheng Y, Nakamura K, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332:600–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Dewan MZ, Galloway AE, Kawashima N, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15:5379–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366:925–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stamell EF, Wolchok JD, Gnjatic S, Lee NY, Brownell I. The abscopal effect associated with a systemic anti-melanoma immune response. Int J Radiat Oncol Biol Phys. 2013;85:293–5.

    Article  PubMed  Google Scholar 

  9. Seyedin SN, Schoenhals JE, Lee DA, et al. Strategies for combining immunotherapy with radiation for anticancer therapy. Immunotherapy. 2015;7(9):967–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tang C, Wang X, Soh H, et al. Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Cancer Immunol Res. 2014;2:831–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys. 2012;83:1306–10.

    Article  CAS  PubMed  Google Scholar 

  12. Filatenkov A, Baker J, Mueller AM, et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin Cancer Res. 2015;21:3727–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev. 2015;41:503–10.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24:207–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest. 2015;125:3384–91.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206:3015–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800.

    Article  CAS  PubMed  Google Scholar 

  19. Lee SJ, Jang BC, Lee SW, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 2006;580:755–62.

    Article  CAS  PubMed  Google Scholar 

  20. Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Science Translational Medicine. 2012;4:127ra37.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74:5458–68.

    Article  CAS  PubMed  Google Scholar 

  22. Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-induced abscopal effect. Cancer Immunol Res. 2015;3:610–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lugade AA, Sorensen EW, Gerber SA, Moran JP, Frelinger JG, Lord EM. Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J Immunol. 2008;180:3132–9.

    Article  CAS  PubMed  Google Scholar 

  24. Wan S, Pestka S, Jubin RG, Lyu YL, Tsai YC, Liu LF. Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells. PLoS One. 2012;7:e32542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Burnette B, Fu YX, Weichselbaum RR. The confluence of radiotherapy and immunotherapy. Front Oncol. 2012;2:143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kwilas AR, Donahue RN, Bernstein MB, Hodge JW. In the field: exploiting the untapped potential of immunogenic modulation by radiation in combination with immunotherapy for the treatment of cancer. Front Oncol. 2012;2:104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Matsumura S, Wang B, Kawashima N, et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol. 2008;181:3099–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Melcher A, Gough M, Todryk S, Vile R. Apoptosis or necrosis for tumor immunotherapy: what’s in a name? J Mol Med (Berl). 1999;77:824–33.

    Article  CAS  Google Scholar 

  29. Kotera Y, Shimizu K, Mule JJ. Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res. 2001;61:8105–9.

    CAS  PubMed  Google Scholar 

  30. McBride WH, Chiang CS, Olson JL, et al. A sense of danger from radiation. Radiat Res. 2004;162:1–19.

    Article  CAS  PubMed  Google Scholar 

  31. Friedman EJ. Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Des. 2002;8:1765–80.

    Article  CAS  PubMed  Google Scholar 

  32. Obeid M, Tesniere A, Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61.

    Article  CAS  PubMed  Google Scholar 

  33. Apetoh L, Ghiringhelli F, Tesniere A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13:1050–9.

    Article  CAS  PubMed  Google Scholar 

  34. Kachikwu EL, Iwamoto KS, Liao YP, et al. Radiation enhances regulatory T cell representation. Int J Radiat Oncol Biol Phys. 2011;81:1128–35.

    Article  PubMed  Google Scholar 

  35. Canney PA, Dean S. Transforming growth factor beta: a promotor of late connective tissue injury following radiotherapy? Br J Radiol. 1990;63:620–3.

    Article  CAS  PubMed  Google Scholar 

  36. Kaur P, Asea A. Radiation-induced effects and the immune system in cancer. Front Oncol. 2012;2:191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wrzesinski SH, Wan YY, Flavell RA. Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clin Cancer Res. 2007;13:5262–70.

    Article  CAS  PubMed  Google Scholar 

  38. Hawinkels LJ, Ten Dijke P. Exploring anti-TGF-beta therapies in cancer and fibrosis. Growth Factors. 2011;29:140–52.

    Article  CAS  PubMed  Google Scholar 

  39. Ivanovic V, Todorovic-Rakovic N, Demajo M, et al. Elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1) in patients with advanced breast cancer: association with disease progression. Eur J Cancer. 2003;39:454–61.

    Article  CAS  PubMed  Google Scholar 

  40. Zhang P, Sun Y, Ma L. ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle. 2015;14:481–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chen L, Gibbons DL, Goswami S, et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014;5:5241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chen Y, Williams J, Ding I, et al. Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol. 2002;12:26–33.

    Article  PubMed  Google Scholar 

  43. Li J, Mu S, Mu L, Zhang X, Pang R, Gao S. Transforming growth factor-beta-1 is a serum biomarker of radiation-induced pneumonitis in esophageal cancer patients treated with thoracic radiotherapy: preliminary results of a prospective study. Onco Targets Ther. 2015;8:1129–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Evans ES, Kocak Z, Zhou SM, et al. Does transforming growth factor-beta1 predict for radiation-induced pneumonitis in patients treated for lung cancer? Cytokine. 2006;35:186–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Stenmark MH, Cai XW, Shedden K, et al. Combining physical and biologic parameters to predict radiation-induced lung toxicity in patients with non-small-cell lung cancer treated with definitive radiation therapy. Int J Radiat Oncol Biol Phys. 2012;84:e217–22.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Wang J, Qiao XY, Lu FH, et al. TGF-beta1 in serum and induced sputum for predicting radiation pneumonitis in patients with non-small cell lung cancer after radiotherapy. Chin J Cancer. 2010;29:325–9.

    Article  PubMed  Google Scholar 

  47. Karre K, Ljunggren HG, Piontek G, Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986;319:675–8.

    Article  CAS  PubMed  Google Scholar 

  48. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9:503–10.

    Article  CAS  PubMed  Google Scholar 

  49. Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature. 2005;436:1186–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kim JY, Son YO, Park SW, et al. Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation. Exp Mol Med. 2006;38:474–84.

    Article  CAS  PubMed  Google Scholar 

  51. Mifune M, Sobue T, Arimoto H, Komoto Y, Kondo S, Tanooka H. Cancer mortality survey in a spa area (Misasa, Japan) with a high radon background. Jpn J Cancer Res. 1992;83:1–5.

    Article  CAS  PubMed  Google Scholar 

  52. Wei LX, Zha YR, Tao ZF, He WH, Chen DQ, Yuan YL. Epidemiological investigation of radiological effects in high background radiation areas of Yangjiang, China. J Radiat Res. 1990;31:119–36.

    Article  CAS  PubMed  Google Scholar 

  53. Kendall GM, Muirhead CR, MacGibbon BH, et al. Mortality and occupational exposure to radiation: first analysis of the National Registry for Radiation Workers. BMJ. 1992;304:220–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Spycher BD, Lupatsch JE, Zwahlen M, et al. Background ionizing radiation and the risk of childhood cancer: a census-based nationwide cohort study. Environ Health Perspect. 2015;123:622–8.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wall BF, Kendall GM, Edwards AA, Bouffler S, Muirhead CR, Meara JR. What are the risks from medical X-rays and other low dose radiation? Br J Radiol. 2006;79:285–94.

    Article  CAS  PubMed  Google Scholar 

  56. Hosoi Y, Ishii K, Yamada S, Ono T, Sakamoto K. Effect of combination treatment of 15 cGy total body irradiation and OK-432 on spontaneous lung metastasis and mitogenic response of splenocytes in mice. Radiat Oncol Investig. 1997;5:283–8.

    Article  CAS  PubMed  Google Scholar 

  57. Hosoi Y, Sakamoto K. Suppressive effect of low dose total body irradiation on lung metastasis: dose dependency and effective period. Radiother Oncol. 1993;26:177–9.

    Article  CAS  PubMed  Google Scholar 

  58. Ren H, Shen J, Tomiyama-Miyaji C, et al. Augmentation of innate immunity by low-dose irradiation. Cell Immunol. 2006;244:50–6.

    Article  CAS  PubMed  Google Scholar 

  59. Kojima S, Nakayama K, Ishida H. Low dose gamma-rays activate immune functions via induction of glutathione and delay tumor growth. J Radiat Res. 2004;45:33–9.

    Article  CAS  PubMed  Google Scholar 

  60. Liu SZ. Cancer control related to stimulation of immunity by low-dose radiation. Dose-Response. 2007;5:39–47.

    Article  CAS  Google Scholar 

  61. Jin SZ, Pan XN, Wu N, Jin GH, Liu SZ. Whole-body low dose irradiation promotes the efficacy of conventional radiotherapy for cancer and possible mechanisms. Dose Response. 2007;5:349–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Burnette B, Weichselbaum RR. The immunology of ablative radiation. Semin Radiat Oncol. 2015;25:40–5.

    Article  PubMed  Google Scholar 

  63. Okuma K, Yamashita H, Niibe Y, Hayakawa K, Nakagawa K. Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report. J Med Case Reports. 2011;5:111.

    Article  PubMed Central  Google Scholar 

  64. Zeng J, See AP, Phallen J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013;86:343–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Camphausen K, Moses MA, Menard C, et al. Radiation abscopal antitumor effect is mediated through p53. Cancer Res. 2003;63:1990–3.

    CAS  PubMed  Google Scholar 

  66. Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203:1259–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174:7516–23.

    Article  CAS  PubMed  Google Scholar 

  68. Lee Y, Auh SL, Wang Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009;114:589–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Barker CA, Postow MA, Khan SA, et al. Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma. Cancer Immunol Res. 2013;1:92–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kiess AP, Wolchok JD, Barker CA, et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys. 2015;92:368–75.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Mathew M, Tam M, Ott PA, et al. Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery. Melanoma Res. 2013;23:191–5.

    Article  CAS  PubMed  Google Scholar 

  72. Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med. 2013;2:899–906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gerber NK, Young RJ, Barker CA, et al. Ipilimumab and whole brain radiation therapy for melanoma brain metastases. J Neurooncol. 2015;121:159–65.

    Article  CAS  PubMed  Google Scholar 

  74. Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189–99.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–7.

    Article  CAS  PubMed  Google Scholar 

  76. Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124:687–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Tang C, Liao Z, Gomez D, et al. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes. Int J Radiat Oncol Biol Phys. 2014;89:1084–91.

    Article  PubMed  Google Scholar 

  78. Hinrichs CS, Palmer DC, Rosenberg SA, Restifo NP. Glucocorticoids do not inhibit antitumor activity of activated CD8+ T cells. J Immunother. 2005;28:517–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Pinkawa M, Djukic V, Klotz J, et al. Hematologic changes during prostate cancer radiation therapy are dependent on the treatment volume. Future Oncol. 2014;10:835–43.

    Article  CAS  PubMed  Google Scholar 

  80. Lawrence YR, Dicker AP. Radiation therapy and the immune system: learning to live together. Future Oncol. 2014;10:777–80.

    Article  CAS  PubMed  Google Scholar 

  81. Finkelstein SE, Salenius S, Mantz CA, et al. Combining immunotherapy and radiation for prostate cancer. Clin Genitourin Cancer. 2015;13:1–9.

    Article  PubMed  Google Scholar 

  82. Golden EB, Demaria S, Schiff PB, Chachoua A, Formenti SC. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res. 2013;1:365–72.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Zumwalt TJ, Goel A. Immunotherapy of metastatic colorectal cancer: prevailing challenges and new perspectives. Curr Colorectal Cancer Rep. 2015;11:125–40.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Zhang GQ, Zhao H, Wu JY, et al. Prolonged overall survival in gastric cancer patients after adoptive immunotherapy. World J Gastroenterol. 2015;21:2777–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zhang GQ, Li F, Sun SJ, et al. Adoptive immunotherapy for small cell lung cancer by expanded activated autologous lymphocytes: a retrospective clinical analysis. Asian Pac J Cancer Prev. 2015;16:1487–94.

    Article  PubMed  Google Scholar 

  86. Wyluda EJ, Cheng J, Schell TD, et al. Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy. Cancer Biol Ther. 2015;16:662–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Massari F, Santoni M, Ciccarese C, et al. PD-1 blockade therapy in renal cell carcinoma: current studies and future promises. Cancer Treat Rev. 2015;41:114–21.

    Article  CAS  PubMed  Google Scholar 

  88. Hiniker SM, Chen DS, Reddy S, et al. A systemic complete response of metastatic melanoma to local radiation and immunotherapy. Transl Oncol. 2012;5:404–7.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Grimaldi AM, Simeone E, Giannarelli D, et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunol. 2014;3:e28780.

    Article  Google Scholar 

  90. Slovin SF, Higano CS, Hamid O, et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013;24:1813–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kwon ED, Drake CG, Scher HI, et al. 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. Lancet Oncol. 2014;15:700–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Hazard LJ, Sause WT, Noyes RD. Combined adjuvant radiation and interferon-alpha 2B therapy in high-risk melanoma patients: the potential for increased radiation toxicity. Int J Radiat Oncol Biol Phys. 2002;52:796–800.

    Article  CAS  PubMed  Google Scholar 

  93. Nguyen NP, Levinson B, Dutta S, et al. Concurrent interferon-alpha and radiation for head and neck melanoma. Melanoma Res. 2003;13:67–71.

    Article  CAS  PubMed  Google Scholar 

  94. Conill C, Jorcano S, Domingo-Domenech J, et al. Toxicity of combined treatment of adjuvant irradiation and interferon alpha2b in high-risk melanoma patients. Melanoma Res. 2007;17:304–9.

    Article  CAS  PubMed  Google Scholar 

  95. Paul E, Muller I, Renner H, Bodeker RH, Cochran AJ. Treatment of locoregional metastases of malignant melanomas with radiotherapy and intralesional beta-interferon injection. Melanoma Res. 2003;13:611–7.

    Article  PubMed  Google Scholar 

  96. Seung SK, Curti BD, Crittenden M, et al. Phase 1 study of stereotactic body radiotherapy and interleukin-2--tumor and immunological responses. Sci Transl Med. 2012;4:137ra74.

    Article  PubMed  Google Scholar 

  97. Ridolfi L, De Rosa F, Granato AM, et al. Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with high-dose interleukin-2: interim analysis data. J Clin Oncol. 2015;33(suppl; abstr e14007).

    Google Scholar 

  98. Ridolfi L, de Rosa F, Ridolfi R, et al. Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with high-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response. J Transl Med. 2014;12:262.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jonathan E. Schoenhals, Maria A. Cortez Ph.D. & Ailin Li M.D., Ph.D.

  2. Department of Radiation Oncology, University of Arizona, Tucson, AZ, USA

    Tijana Skrepnik M.D.

  3. Department of Radiation Oncology, Koc University, Istanbul, Turkey

    Ugur Selek M.D.

  4. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Anderson Central (Y2.5316), 1515 Holcombe Blvd., Unit 0097, Houston, TX, 77030, USA

    Ugur Selek M.D. & James W. Welsh M.D.

  5. Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China

    Ailin Li M.D., Ph.D.

Authors
  1. Jonathan E. Schoenhals
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tijana Skrepnik M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ugur Selek M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria A. Cortez Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ailin Li M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. James W. Welsh M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James W. Welsh M.D. .

Editor information

Editors and Affiliations

  1. MD Anderson Cancer Center, University of Texas, Houston, Texas, USA

    Aung Naing

  2. Baylor College of Medicine-Texas Children’s Hospital, Houston, Texas, USA

    Joud Hajjar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Schoenhals, J.E., Skrepnik, T., Selek, U., Cortez, M.A., Li, A., Welsh, J.W. (2017). Optimizing Radiotherapy with Immunotherapeutic Approaches. In: Naing, A., Hajjar, J. (eds) Immunotherapy. Advances in Experimental Medicine and Biology, vol 995. Springer, Cham. https://doi.org/10.1007/978-3-319-53156-4_3

Download citation

Publish with us

Policies and ethics

Search

Navigation