Abstract
Neutrophils have become recognised as important contributors to the effectiveness of tumour eradication by photodynamic therapy (PDT). In this study, we have used the mouse SCCVII squamous cell carcinoma model to investigate the activity of neutrophils in tumours treated by PDT. Tumour levels of neutrophilic myeloperoxidase (MPO) demonstrated not only a massive and sustained sequestration of these cells in PDT-treated tumours but also revealed their activated state evidenced by the presence of released MPO. Among the adhesion molecules expressed on tumour vascular endothelium, ICAM-1 appears to be of primary importance in the invasion of neutrophils into PDT-treated tumours, because its functional blocking with monoclonal antibodies reduced the tumour cure rate. A marked upregulation of its ligands CD11b/CD18 and CD11c/CD18 found on neutrophils associated with PDT-treated tumours supports this assumption. To evaluate the role of inflammatory cytokines regulating neutrophil activity, neutralising antibodies were given to mice before PDT treatment. The results suggest that IL-1ß activity is critical for the therapeutic outcome, since its neutralisation diminished the cure rates of PDT-treated tumours. No significant effect was observed with anti-IL-6 and anti-TNF-a treatment. Further flow cytometry-based examination of neutrophils found in PDT-treated tumours revealed that these cells express MHC class II molecules, which suggests their engagement as antigen-presenting cells and involvement in the development of antitumour immune response.
Similar content being viewed by others
References
T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, Q. Peng Photodynamic Therapy. J. Natl. Cancer. Inst. 1998 90, 889–905.
M. Korbelik and I. Cecic, Mechanism of tumor destruction by photodynamic therapy, in Handbook of Photochemistry and Photobiology, ed. M. S. A. Abdel-Mottaleb and H. S. Nalwa, American Scientific Publishers, Stevenson Ranch, CA, 2002, in press
I. Cecic, M. Korbelik Mediators of peripheral blood neutrophilia induced by photodynamic therapy of solid tumors. Cancer Lett. 2002 183, 43–51.
M. Korbelik, I. Cecic, J. Sun Relevance of PDT-induced inflammatory response for the outcome of photodynamic therapy. Proc. SPIE–Int. Soc. Opt. Eng. 2001 4257, 19–24.
M. Korbelik, I. Cecic Contribution of myeloid and lymphoid host cells to the curative outcome of mouse sarcoma treatment by photodynamic therapy. Cancer Lett. 1999 137, 91–98.
W. J. A de Vree, M. C. Essers, H. S. de Brujin, W. M. Star, J. F. Koster, W. Sluiter Evidence for an important role of neutrophils in the efficacy of photodynamic therapy in vivo. Cancer Res. 1996 56, 2908–2911.
W. J. A. de Vree, H. S. de Bruijn, R. G. Kraak-Slee, J. F. Koster, W. Sluiter The effect of thrombocytopenia on the efficacy of Photofrin-based photodynamic therapy in vivo. Proc. SPIE–Int. Soc. Opt. Eng. 2001 4156, 79–85.
I. Cecic, C. S. Parkins, M. Korbelik Induction of systemic neutrophil response in mice by photodynamic therapy of solid tumors. Photochem. Photobiol. 2001 74, 712–720.
W. J. A de Vree, M. C. Essers, J. F. Koster, W. Sluiter Role of interleukin 1 and granulocyte colony-stimulating factor in photofrin-based photodynamic therapy of rat rhabdomyosarcoma tumors. Cancer Res. 1997 57, 2555–2558.
H. D. Suit, R. S. Sedlacek, G. Silver, D. Dosoretz Pentobarbital anesthesia and the response of tumor and normal tissue in the C3Hf/Sed mouse to radiation. Radiat. Res. 1985 104, 47–65.
G. Hotter, D. Closa, N. Prats, F. Pi, E. Gelpi, J. Rosello-Catafau Free radical enhancement promotes leucocyte recruitment through a PAF and LTB4 dependent mechanism. Free Radical Biol. Med. 1997 22, 947–954.
M. Korbelik Distribution of disulfonated and tetrasulfonated aluminum phthalocyanine between malignant and host cell populations of a murine fibrosarcoma. J. Photochem. Photobiol., B 1993 20, 173–181.
G. Krosl, M. Korbelik, G. J. Dougherty Induction of immune cell infiltration into murine SCCVII tumor by Photofrin-based photodynamic therapy. Br. J. Cancer 1995 71, 549–555.
S. O. Gollnick, X. Liu, B. Owczarczak, D. A. Musser, B. W. Henderson Altered expression of Interleukin 6 and Interleukin 10 as a result of photodynamic therapy in vivo. Cancer Res. 1997 57, 3904–3909.
P. P. Bradley, D. A. Priebat, R. D. Christensen, G. Rothstein Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J. Invest. Dermatol. 1982 76, 206–209.
S. J. Klebanoff, Phagocytic cells: products of oxygen metabolism, in Inflammation: Basic principles and clinical correlations, ed. J. I. Gallin, I. M. Goldstein and R. Snyderman, Raven Press, New York, 1988, pp. 391–444.
Y. Sibille, H. Y. Reynolds Macrophages and polymorpho-nuclear neutrophils in lung defense and injury. Am. Rev. Respir. Dis. 1991 141, 471–501.
T. M. Carlos, J. M. Harlan Leukocyte-endothelial adhesion molecules. Blood 1994 84, 2068–2101.
S. A. Stacker, T. A. Springer Leukocyte integrin P150,95 (CD11c/CD18) functions as an adhesion molecule binding to a counter-receptor on stimulated endothelium. J. Immunol. 1991 146, 648–655.
S. Evans, W. Matthews, R. Perry, D. Fraker, J. Norton, H. I. Pass Effect of photodynamic therapy on tumor necrosis factor production by murine macrophages. J. Natl. Cancer Inst. 1990 82, 34–39.
S. J. Klebanoff, Oxygen metabolites from phagocytes, in Inflammation: Basic principles and clinical correlations, ed. J. I. Gallin and R. Snyderman, Lippincott Williams & Wilkins, Philadelphia, PA, 1999, pp. 721–768.
G. E. Rainger, A. F. Rowley, G. B. Nash Adhesion-dependent release of elastase from human neutrophils in a novel, flow-based model: specificity of different chemotactic agents. Blood 1998 92, 4819–4827.
H.-A. Lehr, F. Bittinger, C. J. Kirkpatrick Microcirculatory dysfunction in sepsis: a pathogenic basis for therapy. J. Pathol. 2000 190, 373–386.
G. A. Zimmerman, S. M. Prescott, T. M. McIntyre Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol. Today 1992 13, 93–100.
H. Ischikawa, S. Flores, P. R. Kvietys, R. E. Wolf, T. Yoshikawa, D. N. Granger, T. Y. Aw Molecular Mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Circ. Res. 1997 81, 922–931.
A. B. Lentsch, P. A. Ward Regulation of inflammatory vascular damage. J. Pathol. 2000 190, 343–348.
S. J. Weiss Tissue destruction by neutrophils. N. Engl. J. Med. 1989 320, 365–376.
C. A. Dinarello, Interleukin-1: a proinflammatory cytokine, in Inflammation: Basic principles and clinical correlations, ed. J. I. Gallin and R. Snyderman, Lippincott Williams & Wilkins, Philadelphia, PA, 1999, pp. 443–461.
C. A. Dinarello Interleukin-1 and interleukin-1 antagonsim. Blood 1991 77, 1627–1652.
R. A. Gadient, P. H. Patterson Leukemia inhibitory factor, interleukin-6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury. Stem Cells 1999 17, 127–137.
M. Jaattela Biologic activities and mechanisms of action of tumor necrosis factor-a/cachectin. Lab. Invest. 1991 64, 724–742.
M. Korbelik Induction of tumor immunity by photodynamic therapy. J. Clin. Laser Med. Surg. 1996 14, 329–334.
E. J. Gosselin, K. Wardwell, W. F. Rigby, P. M. Guyre Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. J. Immunol. 1993 151, 1482–1490.
N. A. Fanger, C. Liu, P. M. Guyre, K. Wardwell, J. O’Neil, T. L. Guo, T. P. Christian, S. P. Mudzinski, E. J. Gosselin Activation of human T cells by major histocompatibility complex class II expressing neutrophils: proliferation in the presence of superantigen, but not tetanus toxoid. Blood 1997 89, 4128–4135.
M. A. Cassatella Neutrophil-derived proteins: selling cytokines by the pound. Adv. Immunol. 1999 73, 369–509.
A. R. Lloyd, J. J. Oppenheim Poly’s lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunol. Today 1993 13, 169–172.
A. Lichtenstein, J. Kahle Anti-tumor effect of inflammatory neutrophils: characteristics of in vivo generation and in vitro tumor cell lysis. Int. J. Cancer 1985 35, 121–127.
M. A. Vadas, N. A. Nicola, D. Metcalf Activation of antibody-dependent cell mediated cytotoxicity of human neutrophils and eosinophils by separate colony-stimulating factors. J. Immunol. 1983 130, 795–799.
M. P. Colombo, L. Lombardi, A. Stoppacciaro, C. Milani, M. Parenza, B. Bottazi, G. Parmiani Granulocyte colony-stimulating factor (G-CSF) gene transduction in murine adenocarcinoma drives neutrophil-mediated tumor inhibition in vivo. J. Immunol. 1992 149, 113–119.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sun, J., Cecic, I., Parkins, C.S. et al. Neutrophils as inflammatory and immune effectors in photodynamic therapy-treated mouse SCCVII tumours. Photochem Photobiol Sci 1, 690–695 (2002). https://doi.org/10.1039/b204254a
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1039/b204254a