Anti-tumor immune response after photodynamic therapy

Pawel Mroz, Ana P. Castano, Mei X. Wu, Andrew L. Kung, Michael R. Hamblin

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Citation (Scopus)

Abstract

Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naïve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp3+) and potentiate immune response after PDT in the case of tumors that express self-antigens. These data suggest that PDT alone will stimulate a strong immune response when tumors express a robust antigen, and in cases where tumors express a self-antigen, T-reg depletion can unmask the immune response after PDT.

Original languageEnglish (US)
Title of host publication12th World Congress of the International Photodynamic Association - Photodynamic Therapy
Subtitle of host publicationBack to the Future
Volume7380
DOIs
StatePublished - Dec 1 2009
Event12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future - Seattle, WA, United States
Duration: Jun 11 2009Jun 15 2009

Other

Other12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future
CountryUnited States
CitySeattle, WA
Period6/11/096/15/09

Fingerprint

Photodynamic therapy
Photochemotherapy
Tumors
therapy
tumors
antigens
Antigens
Neoplasms
T-cells
mice
Neoplasm Antigens
lymphocytes
Cyclophosphamide
T-Lymphocytes
Epitopes
Autoantigens
beta-Galactosidase
lymphatic system
1-phenyl-3,3-dimethyltriazene
cells

Keywords

  • colon cancer
  • cytotoxic T cells
  • low dose cyclophosphamide
  • photodynamic therapy
  • regulatory T-cells
  • tumor-associated antigen

Cite this

Mroz, P., Castano, A. P., Wu, M. X., Kung, A. L., & Hamblin, M. R. (2009). Anti-tumor immune response after photodynamic therapy. In 12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future (Vol. 7380). [73800F] https://doi.org/10.1117/12.822994

Anti-tumor immune response after photodynamic therapy. / Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future. Vol. 7380 2009. 73800F.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Mroz, P, Castano, AP, Wu, MX, Kung, AL & Hamblin, MR 2009, Anti-tumor immune response after photodynamic therapy. in 12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future. vol. 7380, 73800F, 12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future, Seattle, WA, United States, 6/11/09. https://doi.org/10.1117/12.822994
Mroz P, Castano AP, Wu MX, Kung AL, Hamblin MR. Anti-tumor immune response after photodynamic therapy. In 12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future. Vol. 7380. 2009. 73800F https://doi.org/10.1117/12.822994
Mroz, Pawel ; Castano, Ana P. ; Wu, Mei X. ; Kung, Andrew L. ; Hamblin, Michael R. / Anti-tumor immune response after photodynamic therapy. 12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future. Vol. 7380 2009.
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abstract = "Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime na{\"i}ve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100{\%} of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70{\%} of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100{\%} of cures (versus 0{\%} without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp3+) and potentiate immune response after PDT in the case of tumors that express self-antigens. These data suggest that PDT alone will stimulate a strong immune response when tumors express a robust antigen, and in cases where tumors express a self-antigen, T-reg depletion can unmask the immune response after PDT.",
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