BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy. STUDY DESIGN/ MATERIALS AND METHODS: In the current study we used mice deficient for IL-6, Il6(-/-) , to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity. RESULTS: Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murine colon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6(-/-) mice 24 hours following PDT. CONCLUSIONS: The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered.
BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy. STUDY DESIGN/ MATERIALS AND METHODS: In the current study we used mice deficient for IL-6, Il6(-/-) , to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity. RESULTS: Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murinecolon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6(-/-) mice 24 hours following PDT. CONCLUSIONS: The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered.
Authors: J Usuda; T Okunaka; K Furukawa; T Tsuchida; Y Kuroiwa; Y Ohe; N Saijo; K Nishio; C Konaka; H Kato Journal: Int J Cancer Date: 2001-08-15 Impact factor: 7.396
Authors: Sue S Yom; Theresa M Busch; Joseph S Friedberg; E Paul Wileyto; Deborah Smith; Eli Glatstein; Stephen M Hahn Journal: Photochem Photobiol Date: 2003-07 Impact factor: 3.421
Authors: Barbara W Henderson; Sandra O Gollnick; John W Snyder; Theresa M Busch; Philaretos C Kousis; Richard T Cheney; Janet Morgan Journal: Cancer Res Date: 2004-03-15 Impact factor: 12.701
Authors: S O Gollnick; S S Evans; H Baumann; B Owczarczak; P Maier; L Vaughan; W C Wang; E Unger; B W Henderson Journal: Br J Cancer Date: 2003-06-02 Impact factor: 7.640
Authors: Richard W Davis; Emma Snyder; Joann Miller; Shirron Carter; Cassandra Houser; Astero Klampatsa; Steven M Albelda; Keith A Cengel; Theresa M Busch Journal: Photochem Photobiol Date: 2018-11-26 Impact factor: 3.421
Authors: Mans Broekgaarden; Ruud Weijer; Thomas M van Gulik; Michael R Hamblin; Michal Heger Journal: Cancer Metastasis Rev Date: 2015-12 Impact factor: 9.264
Authors: Stephanie C Casey; Amedeo Amedei; Katia Aquilano; Asfar S Azmi; Fabian Benencia; Dipita Bhakta; Alan E Bilsland; Chandra S Boosani; Sophie Chen; Maria Rosa Ciriolo; Sarah Crawford; Hiromasa Fujii; Alexandros G Georgakilas; Gunjan Guha; Dorota Halicka; William G Helferich; Petr Heneberg; Kanya Honoki; W Nicol Keith; Sid P Kerkar; Sulma I Mohammed; Elena Niccolai; Somaira Nowsheen; H P Vasantha Rupasinghe; Abbas Samadi; Neetu Singh; Wamidh H Talib; Vasundara Venkateswaran; Richard L Whelan; Xujuan Yang; Dean W Felsher Journal: Semin Cancer Biol Date: 2015-04-10 Impact factor: 15.707
Authors: Prathyusha Konda; John A Roque Iii; Liubov M Lifshits; Angelita Alcos; Eissa Azzam; Ge Shi; Colin G Cameron; Sherri A McFarland; Shashi Gujar Journal: Am J Cancer Res Date: 2022-01-15 Impact factor: 6.166
Authors: Mans Broekgaarden; Milan Kos; Freek A Jurg; Adriaan A van Beek; Thomas M van Gulik; Michal Heger Journal: Int J Mol Sci Date: 2015-08-21 Impact factor: 5.923