Systemic Effects

  • Michael Richard Hamblin
  • Caetano Padial Sabino
Chapter
First Online:

Abstract

Photodynamic therapy (PDT) is a clinically approved practice for treatment of cancer and infectious diseases. PDT involves systemic or topical administration of a photosensitizer (PS), followed by irradiation of the target area with light of a wavelength matching the absorption band of the PS. In the presence of oxygen, photochemical reactions trigger the production of reactive oxygen species and, consequently, cell death by oxidative stress. Besides causing direct cytotoxicity to tumor cells, PDT induces destruction of the tumor vasculature releasing pro-inflammatory cytokines. Current literature supports that PDT is able to affect both the innate and adaptive responses of the immune system. In addition, PDT-induced adaptive immunity may attack distant untreated tumor cells and lead to development of antitumor memory immunity, which can potentially avoid the cancer relapse. Conversely, pro-inflammatory activity of PDT can also collaborate to resolve local infections since more neutrophils are recruited to the infected region.

Keywords

Antitumor Immunity Selective Retention Vulval Intraepithelial Neoplasia Tumor Rejection Antigen Immune Stimulation Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Acknowledgments

MR Hamblin was supported by the US NIH Grant R01AI050875.

References

  1. 1.
    Boyle RW, Dolphin D. Structure and biodistribution relationships of photodynamic sensitizers. Photochem Photobiol. 1996;64(3):469–85.CrossRefPubMedGoogle Scholar
  2. 2.
    Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, et al. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011;61(4):250–81.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Garg AD, Krysko DV, Vandenabeele P, Agostinis P. DAMPs and PDT-mediated photo-oxidative stress: exploring the unknown. Photochem Photobiol Sci. 2011;10(5):670–80.CrossRefPubMedGoogle Scholar
  4. 4.
    Maugain E, Sasnouski S, Zorin V, Merlin JL, Guillemin F, Bezdetnaya L. Foscan-based photodynamic treatment in vivo: correlation between efficacy and Foscan accumulation in tumor, plasma and leukocytes. Oncol Rep. 2004;12(3):639–45.PubMedGoogle Scholar
  5. 5.
    Bellnier DA, Greco WR, Parsons JC, Oseroff AR, Kuebler A, Dougherty TJ. An assay for the quantitation of Photofrin in tissues and fluids. Photochem Photobiol. 1997;66(2):237–44.CrossRefPubMedGoogle Scholar
  6. 6.
    Gudgin Dickson EF, Holmes H, Jori G, Kennedy JC, Nadeau P, Pottier RH, et al. On the source of the oscillations observed during in vivo zinc phthalocyanine fluorescence pharmacokinetic measurements in mice. Photochem Photobiol. 1995;61(5):506–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Bellnier DA, Ho YK, Pandey RK, Missert JR, Dougherty TJ. Distribution and elimination of Photofrin II in mice. Photochem Photobiol. 1989;50(2):221–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Little FM, Gomer CJ, Hyman S, Apuzzo ML. Observations in studies of quantitative kinetics of tritium labelled hematoporphyrin derivatives (HpDI and HpDII) in the normal and neoplastic rat brain model. J Neurooncol. 1984;2(4):361–70.CrossRefPubMedGoogle Scholar
  9. 9.
    Schuitmaker JJ, Feitsma RI, Journee-De Korver JG, Dubbelman TM, Pauwels EK. Tissue distribution of bacteriochlorin a labelled with 99mTc-pertechnetate in hamster Greene melanoma. Int J Radiat Biol. 1993;64(4):451–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Frisoli JK, Tudor EG, Flotte TJ, Hasan T, Deutsch TF, Schomacker KT. Pharmacokinetics of a fluorescent drug using laser-induced fluorescence. Cancer Res. 1993;53(24):5954–61.PubMedGoogle Scholar
  11. 11.
    Sheng C, Pogue BW, Wang E, Hutchins JE, Hoopes PJ. Assessment of photosensitizer dosimetry and tissue damage assay for photodynamic therapy in advanced-stage tumors. Photochem Photobiol. 2004;79(6):520–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Bellnier DA, Dougherty TJ. A preliminary pharmacokinetic study of intravenous Photofrin in patients. J Clin Laser Med Surg. 1996;14(5):311–4.PubMedGoogle Scholar
  13. 13.
    Moriwaki SI, Misawa J, Yoshinari Y, Yamada I, Takigawa M, Tokura Y. Analysis of photosensitivity in Japanese cancer-bearing patients receiving photodynamic therapy with porfimer sodium (Photofrin). Photodermatol Photoimmunol Photomed. 2001;17(5):241–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Bellnier DA, Greco WR, Loewen GM, Nava H, Oseroff AR, Pandey RK, et al. Population pharmacokinetics of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a in cancer patients. Cancer Res. 2003;63(8):1806–13.PubMedGoogle Scholar
  15. 15.
    Jones HJ, Vernon DI, Brown SB. Photodynamic therapy effect of m-THPC (Foscan) in vivo: correlation with pharmacokinetics. Br J Cancer. 2003;89(2):398–404.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Egorin MJ, Zuhowski EG, Sentz DL, Dobson JM, Callery PS, Eiseman JL. Plasma pharmacokinetics and tissue distribution in CD2F1 mice of Pc4 (NSC 676418), a silicone phthalocyanine photodynamic sensitizing agent. Cancer Chemother Pharmacol. 1999;44(4):283–94.CrossRefPubMedGoogle Scholar
  17. 17.
    Brun PH, DeGroot JL, Dickson EF, Farahani M, Pottier RH. Determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide (WST09) in EMT6 tumour-bearing Balb/c mice using graphite furnace atomic absorption spectroscopy. Photochem Photobiol Sci. 2004;3(11–12):1006–10.CrossRefPubMedGoogle Scholar
  18. 18.
    Woodburn KW, Stylli S, Hill JS, Kaye AH, Reiss JA, Phillips DR. Evaluation of tumour and tissue distribution of porphyrins for use in photodynamic therapy. Br J Cancer. 1992;65(3):321–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Richter AM, Cerruti-Sola S, Sternberg ED, Dolphin D, Levy JG. Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice. J Photochem Photobiol B. 1990;5(2):231–44.CrossRefPubMedGoogle Scholar
  20. 20.
    Hamblin MR, Newman EL. On the mechanism of the tumour-localising effect in photodynamic therapy. J Photochem Photobiol B. 1994;23(1):3–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Jori G. In vivo transport and pharmacokinetic behavior of tumour photosensitizers. Ciba Found Symp. 1989;146:78–86.PubMedGoogle Scholar
  22. 22.
    Larroque C, Pelegrin A, Van Lier JE. Serum albumin as a vehicle for zinc phthalocyanine: photodynamic activities in solid tumour models. Br J Cancer. 1996;74(12):1886–90.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kessel D, Poretz RD. Sites of photodamage induced by photodynamic therapy with a chlorin e6 triacetoxymethyl ester (CAME). Photochem Photobiol. 2000;71(1):94–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Kongshaug M, Moan J, Brown SB. The distribution of porphyrins with different tumour localising ability among human plasma proteins. Br J Cancer. 1989;59(2):184–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Maziere JC, Santus R, Morliere P, Reyftmann JP, Candide C, Mora L, et al. Cellular uptake and photosensitizing properties of anticancer porphyrins in cell membranes and low and high density lipoproteins. J Photochem Photobiol B. 1990;6(1–2):61–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Jori G, Reddi E. The role of lipoproteins in the delivery of tumour-targeting photosensitizers. Int J Biochem. 1993;25(10):1369–75.CrossRefPubMedGoogle Scholar
  27. 27.
    Korbelik M. Low density lipoprotein receptor pathway in the delivery of Photofrin: how much is it relevant for selective accumulation of the photosensitizer in tumors? J Photochem Photobiol B. 1992;12(1):107–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Yuan F, Leunig M, Berk DA, Jain RK. Microvascular permeability of albumin, vascular surface area, and vascular volume measured in human adenocarcinoma LS174T using dorsal chamber in SCID mice. Microvasc Res. 1993;45(3):269–89.CrossRefPubMedGoogle Scholar
  29. 29.
    Allison BA, Pritchard PH, Levy JG. Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative. Br J Cancer. 1994;69(5):833–9.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Pottier R, Kennedy JC. The possible role of ionic species in selective biodistribution of photochemotherapeutic agents toward neoplastic tissue. J Photochem Photobiol B. 1990;8(1):1–16.CrossRefPubMedGoogle Scholar
  31. 31.
    Freitas I. Lipid accumulation: the common feature to photosensitizer-retaining normal and malignant tissues [news]. J Photochem Photobiol B. 1990;7(2–4):359–61.CrossRefPubMedGoogle Scholar
  32. 32.
    Korbelik M, Krosl G. Photofrin accumulation in malignant and host cell populations of a murine fibrosarcoma. Photochem Photobiol. 1995;62(1):162–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Henderson BW, Waldow SM, Mang TS, Potter WR, Malone PB, Dougherty TJ. Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res. 1985;45(2):572–6.PubMedGoogle Scholar
  34. 34.
    Henderson BW, Fingar VH. Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem Photobiol. 1989;49(3):299–304.CrossRefPubMedGoogle Scholar
  35. 35.
    Castellani A, Pace GP, Concioli M. Photodynamic effect of haematoporphyrin on blood microcirculation. J Pathol Bacteriol. 1963;86:99–102.CrossRefPubMedGoogle Scholar
  36. 36.
    Star WM, Marijnissen HP, van den Berg-Blok AE, Versteeg JA, Franken KA, Reinhold HS. Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. Cancer Res. 1986;46(5):2532–40.PubMedGoogle Scholar
  37. 37.
    Bhuvaneswari R, Gan YY, Soo KC, Olivo M. The effect of photodynamic therapy on tumor angiogenesis. Cell Mol Life Sci. 2009;66(14):2275–83.CrossRefPubMedGoogle Scholar
  38. 38.
    Tseng MT, Reed MW, Ackermann DM, Schuschke DA, Wieman TJ, Miller FN. Photodynamic therapy induced ultrastructural alterations in microvasculature of the rat cremaster muscle. Photochem Photobiol. 1988;48(5):675–81.CrossRefPubMedGoogle Scholar
  39. 39.
    Gomer CJ, Rucker N, Murphree AL. Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res. 1988;48(16):4539–42.PubMedGoogle Scholar
  40. 40.
    West CM, West DC, Kumar S, Moore JV. A comparison of the sensitivity to photodynamic treatment of endothelial and tumour cells in different proliferative states. Int J Radiat Biol. 1990;58(1):145–56.CrossRefPubMedGoogle Scholar
  41. 41.
    Fingar VH, Wieman TJ, Wiehle SA, Cerrito PB. The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion. Cancer Res. 1992;52(18):4914–21.PubMedGoogle Scholar
  42. 42.
    Fingar VH, Kik PK, Haydon PS, Cerrito PB, Tseng M, Abang E, et al. Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD). Br J Cancer. 1999;79(11–12):1702–8.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    He C, Agharkar P, Chen B. Intravital microscopic analysis of vascular perfusion and macromolecule extravasation after photodynamic vascular targeting therapy. Pharm Res. 2008;25(8):1873–80.CrossRefPubMedGoogle Scholar
  44. 44.
    Debefve E, Cheng C, Schaefer SC, Yan H, Ballini JP, van den Bergh H, et al. Photodynamic therapy induces selective extravasation of macromolecules: insights using intravital microscopy. J Photochem Photobiol B, Biol. 2010;98(1):69–76.CrossRefPubMedGoogle Scholar
  45. 45.
    Khurana M, Moriyama EH, Mariampillai A, Wilson BC. Intravital high-resolution optical imaging of individual vessel response to photodynamic treatment. J Biomed Opt. 2008;13(4):040502.CrossRefPubMedGoogle Scholar
  46. 46.
    Madar-Balakirski N, Tempel-Brami C, Kalchenko V, Brenner O, Varon D, Scherz A, et al. Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP) with Tookad. PLoS One. 2010;5(4):e10282.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Dolmans DE, Kadambi A, Hill JS, Waters CA, Robinson BC, Walker JP, et al. Vascular accumulation of a novel photosensitizer, MV6401, causes selective thrombosis in tumor vessels after photodynamic therapy. Cancer Res. 2002;62(7):2151–6.PubMedGoogle Scholar
  48. 48.
    Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, et al. Photodynamic therapy. J Natl Cancer Inst. 1998;90(12):889–905.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Korbelik M. PDT-associated host response and its role in the therapy outcome. Lasers Surg Med. 2006;38(5):500–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol. 2015;6:588.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Magna M, Pisetsky DS. The alarmin properties of DNA and DNA-associated nuclear proteins. Clin Ther. 2016;38(5):1029–41.CrossRefPubMedGoogle Scholar
  52. 52.
    Bhargava A, Mishra D, Banerjee S, Mishra PK. Dendritic cell engineering for tumor immunotherapy: from biology to clinical translation. Immunotherapy. 2012;4(7):703–18.CrossRefPubMedGoogle Scholar
  53. 53.
    Henderson BW, Gollnick SO. Mechanistic principles of photodynamic therapy. In: Vo-Dinh T, editor. Biomedical photonics handbook. Boca Raton: CRC Press; 2003. p. 36.1–27.Google Scholar
  54. 54.
    Oleinick NL, Evans HH. The photobiology of photodynamic therapy: cellular targets and mechanisms. Radiat Res. 1998;150(5 Suppl):S146–56.CrossRefPubMedGoogle Scholar
  55. 55.
    Gollnick SO, Owczarczak B, Maier P. Photodynamic therapy and anti-tumor immunity. Lasers Surg Med. 2006;38(5):509–15.CrossRefPubMedGoogle Scholar
  56. 56.
    Korbelik M, Sun J, Cecic I. Photodynamic therapy-induced cell surface expression and release of heat shock proteins: relevance for tumor response. Cancer Res. 2005;65(3):1018–26.PubMedGoogle Scholar
  57. 57.
    Korbelik M, Stott B, Sun J. Photodynamic therapy-generated vaccines: relevance of tumour cell death expression. Br J Cancer. 2007;97(10):1381–7.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Vabulas RM, Wagner H, Schild H. Heat shock proteins as ligands of toll-like receptors. Curr Top Microbiol Immunol. 2002;270:169–84.PubMedGoogle Scholar
  59. 59.
    Gomer CJ, Ryter SW, Ferrario A, Rucker N, Wong S, Fisher AM. Photodynamic therapy-mediated oxidative stress can induce expression of heat shock proteins. Cancer Res. 1996;56(10):2355–60.PubMedGoogle Scholar
  60. 60.
    Gollnick SO, Kabingu E, Kousis PC, Henderson BW. Stimulation of the host immune response by photodynamic therapy (PDT). Proc SPIE. 2004;5319:60–70.CrossRefGoogle Scholar
  61. 61.
    Stott B, Korbelik M. Activation of complement C3, C5, and C9 genes in tumors treated by photodynamic therapy. Cancer Immunol Immunother. 2007;56(5):649–58.CrossRefPubMedGoogle Scholar
  62. 62.
    Krosl G, Korbelik M, Dougherty GJ. Induction of immune cell infiltration into murine SCCVII tumour by photofrin-based photodynamic therapy. Br J Cancer. 1995;71(3):549–55.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Korbelik M, Cecic I. Contribution of myeloid and lymphoid host cells to the curative outcome of mouse sarcoma treatment by photodynamic therapy. Cancer Lett. 1999;137(1):91–8.CrossRefPubMedGoogle Scholar
  64. 64.
    de Vree WJ, Essers MC, Koster JF, Sluiter W. Role of interleukin 1 and granulocyte colony-stimulating factor in photofrin-based photodynamic therapy of rat rhabdomyosarcoma tumors. Cancer Res. 1997;57(13):2555–8.PubMedGoogle Scholar
  65. 65.
    Kousis PC, Henderson BW, Maier PG, Gollnick SO. Photodynamic therapy enhancement of antitumor immunity is regulated by neutrophils. Cancer Res. 2007;67(21):10501–10.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Korbelik M, Cecic I. Mechanism of tumor destruction by photodynamic therapy. In: Nalwa HS, editor. Handbook of photochemistry and photobiology. Stevenson Ranch: American Scientific Publishers; 2003. p. 39–77.Google Scholar
  67. 67.
    Sun J, Cecic I, Parkins CS, Korbelik M. Neutrophils as inflammatory and immune effectors in photodynamic therapy-treated mouse SCCVII tumours. Photochem Photobiol Sci. 2002;1(9):690–5.CrossRefPubMedGoogle Scholar
  68. 68.
    Gollnick SO, Evans SS, Baumann H, Owczarczak B, Maier P, Vaughan L, et al. Role of cytokines in photodynamic therapy-induced local and systemic inflammation. Br J Cancer. 2003;88(11):1772–9.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Hunt DW, Levy JG. Immunomodulatory aspects of photodynamic therapy. Expert Opin Investig Drugs. 1998;7(1):57–64.CrossRefPubMedGoogle Scholar
  70. 70.
    Yusuf N, Katiyar SK, Elmets CA. The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4+ and CD8+ T cells and can be adoptively transferred to naive recipients. Photochem Photobiol. 2008;84(2):366–70.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Korbelik M, Krosl G, Krosl J, Dougherty GJ. The role of host lymphoid populations in the response of mouse EMT6 tumor to photodynamic therapy. Cancer Res. 1996;56(24):5647–52.PubMedGoogle Scholar
  72. 72.
    Canti GL, Lattuada D, Nicolin A, Taroni P, Valentini G, Cubeddu R. Immunopharmacology studies on photosensitizers used in photodynamic therapy. Proc SPIE. 1994;2078:268–75.CrossRefGoogle Scholar
  73. 73.
    Korbelik M, Dougherty GJ. Photodynamic therapy-mediated immune response against subcutaneous mouse tumors. Cancer Res. 1999;59(8):1941–6.PubMedGoogle Scholar
  74. 74.
    Mroz P, Szokalska A, Wu MX, Hamblin MR. Photodynamic therapy of tumors can lead to development of systemic antigen-specific immune response. PLoS One. 2010;5(12):e15194.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Mroz P, Vatansever F, Muchowicz A, Hamblin MR. Photodynamic therapy of murine mastocytoma induces specific immune responses against the cancer/testis antigen P1A. Cancer Res. 2013;73(21):6462–70.CrossRefPubMedGoogle Scholar
  76. 76.
    Maeurer MJ, Gollin SM, Storkus WJ, Swaney W, Karbach J, Martin D, et al. Tumor escape from immune recognition: loss of HLA-A2 melanoma cell surface expression is associated with a complex rearrangement of the short arm of chromosome 6. Clin Cancer Res. 1996;2(4):641–52.PubMedGoogle Scholar
  77. 77.
    Wachowska M, Gabrysiak M, Muchowicz A, Bednarek W, Barankiewicz J, Rygiel T, et al. 5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy. Eur J Cancer. 2014;50(7):1370–81.Google Scholar
  78. 78.
    Abdel-Hady ES, Martin-Hirsch P, Duggan-Keen M, Stern PL, Moore JV, Corbitt G, et al. Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Res. 2001;61(1):192–6.PubMedGoogle Scholar
  79. 79.
    Kabingu E, Vaughan L, Owczarczak B, Ramsey KD, Gollnick SO. CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells. Br J Cancer. 2007;96(12):1839–48.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Henderson BW, Gollnick SO, Snyder JW, Busch TM, Kousis PC, Cheney RT, et al. Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors. Cancer Res. 2004;64(6):2120–6.CrossRefPubMedGoogle Scholar
  81. 81.
    Reis e Sousa C. Activation of dendritic cells: translating innate into adaptive immunity. Curr Opin Immunol. 2004;16(1):21–5.CrossRefPubMedGoogle Scholar
  82. 82.
    Benvenuti F. The dendritic cell synapse: a life dedicated to T cell activation. Front Immunol. 2016;7:70.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Sur BW, Nguyen P, Sun CH, Tromberg BJ, Nelson EL. Immunophototherapy using PDT combined with rapid intratumoral dendritic cell injection. Photochem Photobiol. 2008;84(5):1257–64.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Castellino F, Germain RN. Cooperation between CD4+ and CD8+ T cells: when, where, and how. Annu Rev Immunol. 2006;24:519–40.CrossRefPubMedGoogle Scholar
  85. 85.
    Gollnick SO, Vaughan L, Henderson BW. Generation of effective antitumor vaccines using photodynamic therapy. Cancer Res. 2002;62(6):1604–8.PubMedGoogle Scholar
  86. 86.
    Korbelik M, Sun J. Photodynamic therapy-generated vaccine for cancer therapy. Cancer Immunol Immunother. 2006;55(8):900–9.CrossRefPubMedGoogle Scholar
  87. 87.
    Korbelik M, Merchant S, Huang N. Exploitation of immune response-eliciting properties of hypocrellin photosensitizer SL052-based photodynamic therapy for eradication of malignant tumors. Photochem Photobiol. 2009;85(6):1418–24.CrossRefPubMedGoogle Scholar
  88. 88.
    Jalili A, Makowski M, Switaj T, Nowis D, Wilczynski GM, Wilczek E, et al. Effective photoimmunotherapy of murine colon carcinoma induced by the combination of photodynamic therapy and dendritic cells. Clin Cancer Res. 2004;10(13):4498–508.CrossRefPubMedGoogle Scholar
  89. 89.
    Gomer CJ, Ferrario A, Murphree AL. The effect of localized porphyrin photodynamic therapy on the induction of tumour metastasis. Br J Cancer. 1987;56(1):27–32.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    van Duijnhoven FH, Aalbers RI, Rovers JP, Terpstra OT, Kuppen PJ. Immunological aspects of photodynamic therapy of liver tumors in a rat model for colorectal cancer. Photochem Photobiol. 2003;78(3):235–40.CrossRefPubMedGoogle Scholar
  91. 91.
    Dragieva G, Hafner J, Dummer R, Schmid-Grendelmeier P, Roos M, Prinz BM, et al. Topical photodynamic therapy in the treatment of actinic keratoses and Bowen’s disease in transplant recipients. Transplantation. 2004;77(1):115–21.CrossRefPubMedGoogle Scholar
  92. 92.
    Thong PS, Ong KW, Goh NS, Kho KW, Manivasager V, Bhuvaneswari R, et al. Photodynamic-therapy-activated immune response against distant untreated tumours in recurrent angiosarcoma. Lancet Oncol. 2007;8(10):950–2.CrossRefPubMedGoogle Scholar
  93. 93.
    Thong PS, Olivo M, Kho KW, Bhuvaneswari R, Chin WW, Ong KW, et al. Immune response against angiosarcoma following lower fluence rate clinical photodynamic therapy. J Environ Pathol Toxicol Oncol. 2008;27(1):35–42.CrossRefPubMedGoogle Scholar
  94. 94.
    Friedberg JS, Mick R, Stevenson JP, Zhu T, Busch TM, Shin D, et al. Phase II trial of pleural photodynamic therapy and surgery for patients with non-small-cell lung cancer with pleural spread. J Clin Oncol. 2004;22(11):2192–201.CrossRefPubMedGoogle Scholar
  95. 95.
    Kabingu E, Oseroff AR, Wilding GE, Gollnick SO. Enhanced systemic immune reactivity to a basal cell carcinoma associated antigen following photodynamic therapy. Clin Cancer Res. 2009;15(13):4460–6.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Gad F, Zahra T, Francis KP, Hasan T, Hamblin MR. Targeted photodynamic therapy of established soft-tissue infections in mice. Photochem Photobiol Sci. 2004;3(5):451–8.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Tanaka M, Mroz P, Dai T, Huang L, Morimoto Y, Kinoshita M, et al. Photodynamic therapy can induce a protective innate immune response against murine bacterial arthritis via neutrophil accumulation. PLoS One. 2012;7(6):e39823.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Gryson O. Servier medical art France: servier; 2016 [Available from: http://www.servier.com/Powerpoint-image-bank.

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Michael Richard Hamblin
    • 1
    • 2
    • 3
  • Caetano Padial Sabino
    • 4
    • 5
    • 6
    • 7
  1. 1.Wellman Center for PhotomedicineMassachusetts General HospitalBostonUSA
  2. 2.Department of DermatologyHarvard Medical SchoolBostonUSA
  3. 3.Harvard-MIT Division of Health Sciences and TechnologyCambridgeUSA
  4. 4.Department of Microbiology, Institute for Biomedical SciencesUniversity of São PauloSao PauloBrazil
  5. 5.Department of Clinical Analysis, School of Pharmaceutical SciencesUniversity of São PauloSao PauloBrazil
  6. 6.Center for Lasers and Applications, Nuclear and Energy Research Institute, National Commission for Nuclear EnergySao PauloBrazil
  7. 7.Department of Medical Biophysics, Princess Margaret Cancer InstituteUniversity of TorontoTorontoCanada

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