The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model
Open accessAbstract
Photodynamic therapy (PDT) is a modality for the treatment of cancer involving excitation of nontoxic photosensitizers with harmless visible light-producing cytotoxic reactive oxygen species. PDT causes apoptosis and necrosis of tumor cells, destruction of the tumor blood supply, and activation of the immune system. The objective of this study was to compare in an animal model of metastatic cancer PDT alone and PDT combined with low-dose cyclophosphamide (CY) a treatment that has been proposed to deplete regulatory T cells (T-regs) and increase the immune response to some tumors. We used J774 tumors (a highly metastatic reticulum cell sarcoma line) and PDT with benzoporphyrin derivative monoacid ring A, verteporfin for injection (BPD; 1-mg/kg injected i.v. followed after 15 min by 150 J/cm 2 of 690-nm light). CY (50 or 150 mg/kg i.p.) was injected 48 h before light delivery. PDT alone led to tumor regressions and a survival advantage but no permanent cures were obtained. BPD–PDT in combination with low-dose CY (but not high-dose CY) led to 70% permanent cures. Low-dose CY alone gave no permanent cures but did provide a survival advantage and was shown to reduce CD4+FoxP3+ T-regs in lymph nodes, whereas high-dose CY reduced other lymphocyte classes as well. Cured animals were rechallenged with J774 cells, and the tumors were rejected in 71% of mice. Cured mice had tumor-specific T cells in spleens as determined by a 51 Cr release assay. We conclude that low-dose CY depletes T-regs and potentiates BPD–PDT, leading to tumor cures and memory immunity.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“It is generally agreed that apart from the direct cellular cytotoxicity, two other important factors contribute to the overall PDT effect: the vascular shutdown and local inflammatory reaction [1,2,3,4].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [1]
Citations
Cites
Photodynamic therapy and anti-tumour immunity
Castaño, A. P., Mróz, P., & Hamblin, M. R. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1894 · Cited by 2,685
Self-citationCastaño, A. P., Demidova, T. N., & Hamblin, M. R. (2004) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/s1572-1000(05)00007-4 · Cited by 2,059
Self-citationStimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance
Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., & Sakaguchi, S. (2002) · Nature Immunology · doi:10.1038/ni759 · Cited by 1,729
Sutmuller, R. P. M., van Duivenvoorde, L. M., van Elsas, A., Schumacher, T. N. M., Wildenberg, M. E., Allison, J. P., Toes, R. E. M., Offringa, R., & Melief, C. J. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.823 · Cited by 1,008
Ziegler, S. F. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090547 · Cited by 921
Lutsiak, M. E. C., Semnani, R. T., De Pascalis, R., Kashmiri, S. V. S., Schlom, J., & Sabzevari, H. (2005) · Blood · doi:10.1182/blood-2004-06-2410 · Cited by 903
Ghiringhelli, F., Larmonier, N., Schmitt, E., Parcellier, A., Cathelin, D., Garrido, C., Chauffert, B., Solary, É., Bonnotte, B., & Martin, F. (2004) · European Journal of Immunology · doi:10.1002/eji.200324181 · Cited by 878
Castaño, A. P., Demidova, T. N., & Hamblin, M. R. (2005) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/s1572-1000(05)00030-x · Cited by 797
Self-citationBeyer, M., & Schultze, J. L. (2006) · Blood · doi:10.1182/blood-2006-02-002774 · Cited by 741
North, R. J. (1982) · The Journal of Experimental Medicine · doi:10.1084/jem.155.4.1063 · Cited by 657
Castaño, A. P., Demidova, T. N., & Hamblin, M. R. (2005) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/s1572-1000(05)00060-8 · Cited by 551
Self-citationAn Update on Photodynamic Therapy Applications
Dougherty, T. J. (2002) · Journal of Clinical Laser Medicine & Surgery · doi:10.1089/104454702753474931 · Cited by 547
Control of T‐cell activation by CD4+ CD25+ suppressor T cells
Shevach, E. M., McHugh, R. S., Piccirillo, C. A., & Thornton, A. M. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1820104.x · Cited by 544
Concomitant Tumor Immunity to a Poorly Immunogenic Melanoma Is Prevented by Regulatory T Cells
Turk, M. J., Guevara-Patino, J. A., Rizzuto, G. A., Engelhorn, M. E., & Houghton, A. N. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041130 · Cited by 537
Yu, P., Lee, Y., Liu, W., Krausz, T. N., Chong, A. S., Schreiber, H. W., & Fu, Y. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041684 · Cited by 441
Reticulum Cell Sarcoma: An Effector Cell in Antibody-Dependent Cell-Mediated Immunity
Ralph, P., Prichard, J. G., & Cohn, M. (1975) · The Journal of Immunology · doi:10.4049/jimmunol.114.2_part_2.898 · Cited by 422
Henderson, B. W., Waldow, S. M., Mang, T. S., Potter, W. R., Pb, M., & Dougherty, T. J. (1985) · PubMed · Cited by 399
Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response
Ercolini, A. M., Ladle, B. H., Manning, E. A., Pfannenstiel, L. W., Armstrong, T. D., Machiels, J., Bieler, J. G., Emens, L. A., Reilly, R. T., & Jaffee, E. M. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042167 · Cited by 398
Role of cytokines in photodynamic therapy-induced local and systemic inflammation
Gollnick, S., Evans, S. S., Baumann, H., Owczarczak, B., Maier, P., Vaughan, L. A., Wang, W.-C., Unger, E., & Henderson, B. W. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600864 · Cited by 352
Regulatory T cells in immune surveillance and treatment of cancer
Yamaguchi, T., & Sakaguchi, S. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.11.005 · Cited by 269
Induction of Tumor Immunity by Photodynamic Therapy
Korbelik, M. (1996) · Journal of Clinical Laser Medicine & Surgery · doi:10.1089/clm.1996.14.329 · Cited by 256
Photodynamic therapy-mediated immune response against subcutaneous mouse tumors.
Korbelik, M., & Dougherty, G. J. (1999) · PubMed · Cited by 209
Tanaka, H., Tanaka, J., Kjærgaard, J., & Shu, S. (2002) · Journal of Immunotherapy · doi:10.1097/00002371-200205000-00003 · Cited by 205
The role of host lymphoid populations in the response of mouse EMT6 tumor to photodynamic therapy.
Korbelik, M., Krosl, G., Krošl, J., & Dougherty, G. J. (1996) · PubMed · Cited by 165
Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide
Motoyoshi, Y., Kaminoda, K., Saitoh, O., Hamasaki, K., Nakao, K., Ishii, N., Nagayama, Y., & Eguchi, K. (2006) · Oncology Reports · doi:10.3892/or.16.1.141 · Cited by 161
Targeting of the vascular system of solid tumours by photodynamic therapy (PDT)
Abels, C. (2004) · Photochemical & Photobiological Sciences · doi:10.1039/b314241h · Cited by 158
Prasad, S. J., Farrand, K. J., Matthews, S. A., Chang, J. H., McHugh, R. S., & Ronchese, F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.1.90 · Cited by 153
Awwad, M., & North, R. J. (1989) · PubMed · Cited by 149
Photodynamic therapy and anti‐tumor immunity
Gollnick, S. O., Owczarczak, B., & Maier, P. G. (2006) · Lasers in Surgery and Medicine · doi:10.1002/lsm.20362 · Cited by 141
Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy
Chen, B., Pogue, B. W., Hoopes, P. J., & Hasan, T. G. (2005) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2004.08.006 · Cited by 125
Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model
Matar, P., Rozados, V. R., Gervasoni, S. I., & Scharovsky, O. G. (2002) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-001-0237-3 · Cited by 119
Antitumor immunity induced by laser immunotherapy and its adoptive transfer.
Chen, W. R., Singhal, A. K., Liu, H., & Nordquist, R. E. (2001) · PubMed · Cited by 114
Effect of different components of laser immunotherapy in treatment of metastatic tumors in rats.
Chen, W. R., Liu, H., Ritchey, J. W., Bartels, K. E., Lucroy, M. D., & Nordquist, R. E. (2002) · PubMed · Cited by 109
Zhang, Q., Kang, X., & Zhao, W. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.044 · Cited by 108
In situ photoimmunotherapy: a tumour-directed treatment for melanoma
Naylor, M. F., Chen, W. R., Teague, T. K., Perry, L., & Nordquist, R. E. (2006) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2006.07514.x · Cited by 94
Loeffler, M. W., Krüger, J. A., & Reisfeld, R. A. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0646 · Cited by 88
Induction of Systemic Neutrophil Response in Mice by Photodynamic Therapy of Solid Tumors¶
Cecić, I., Parkins, C. S., & Korbelik, M. (2001) · Photochemistry and Photobiology · doi:10.1562/0031-8655(2001)0740712iosnri2.0.co2 · Cited by 83
Role of Cytokine Therapy in 2006 and Beyond for Metastatic Renal Cell Cancer
Parton, M., Gore, M. E., & Eisen, T. G. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.1638 · Cited by 79
Current developments of immunotherapy in the clinic
Antonia, S. J., Mulé, J. J., & Weber, J. S. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.01.012 · Cited by 73
Enhancement of laser cancer treatment by a chitosan-derived immunoadjuvant
Chen, W. R., Korbelik, M., Bartels, K. E., Liu, H., Sun, J., & Nordquist, R. E. (2004) · Photochemistry and Photobiology · doi:10.1562/2004-07-20-ra-236 · Cited by 69
Seshadri, M., Spernyak, J. A., Mazurchuk, R. V., Camacho, S. H., Oseroff, A. R., Cheney, R. T., & Bellnier, D. A. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2703 · Cited by 62
Molecular aspects of regulatory T cell development
Fontenot, J. D. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2003.12.002 · Cited by 59
Cell subpopulations dispersed from solid tumours and separated by centrifugal elutriation
Siemann, D. W., Lord, E. M., Keng, P. C., & Wheeler, K. T. (1981) · British Journal of Cancer · doi:10.1038/bjc.1981.154 · Cited by 56
Mechanism of antimetastatic immunopotentiation by low-dose cyclophosphamide
Matar, P., Rozados, V. R., González, A. D., Dlugovitzky, D. G., Bonfil, R. D., & Scharovsky, O. G. (2000) · European Journal of Cancer · doi:10.1016/s0959-8049(00)00044-7 · Cited by 49
Control of T Cell Activation by CD4 + CD25 + Suppressor T Cells
Shevach, E. M., Piccirillo, C. A., Thornton, A. M., & McHugh, R. S. (2003) · Novartis Foundation symposium · doi:10.1002/0470871628.ch3 · Cited by 47
Enhancement of Laser Cancer Treatment by a Chitosan-derived Immunoadjuvant¶
Chen, W. R., Korbelik, M., Bartels, K. E., Liu, H., Sun, J., & Nordquist, R. E. (2005) · Photochemistry and Photobiology · doi:10.1562/2004-07-20-ra-236.1 · Cited by 45
Cancer Vaccines: An Old Idea Comes of Age
Emens, L. A., & Jaffee, E. M. (2003) · Cancer Biology & Therapy · doi:10.4161/cbt.217 · Cited by 39
A New Twist on Autologous Cancer Vaccines
Emens, L. A. (2003) · Cancer Biology & Therapy · doi:10.4161/cbt.2.2.283 · Cited by 35
CD4+ T Cell Responses to Self- and Mutated p53 Determinants During Tumorigenesis in Mice
Fedoseyeva, E. V., Boisgérault, F., Anosova, N. G., Wollish, W., Arlotta, P., Jensen, P. E., Ono, S. J., & Bénichou, G. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.11.5641 · Cited by 30
The changes of CD4+CD25+/CD4+ proportion in spleen of tumor-bearing BALB/c mice
Liu, J., Zhang, X., Ding, Y., Peng, R., Cheng, X., Zhang, N.-H., Xia, J., & Zeng, Y. (2005) · Journal of Translational Medicine · doi:10.1186/1479-5876-3-5 · Cited by 26
Ray, P. K., & Raychaudhuri, S. (1981) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/67.6.1341 · Cited by 21
T cell-mediated immunotherapy of metastases: state of the art in 2005
Schirrmacher, V. (2005) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.5.8.1051 · Cited by 15
Development of cancer vaccines to activate cytotoxic T lymphocytes
Durrant, L., & Ramage, J. M. (2005) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.5.4.555 · Cited by 14
Holoprosencephaly and cyclopia visualized by two- and three-dimensional prenatal ultrasound.
Lee, Y.-Y., Lin, M.-T., Lee, M., & Lin, L. (2002) · PubMed · Cited by 12
Biological response modifiers in cancer therapy.
Gupta, S., & Kanodia, A. K. (2002) · PubMed · Cited by 10
Gene therapy of cancer: induction of anti-tumor immunity.
ChengQian, & JesusPrieto (2004) · PubMed · Cited by 8
Circumvention Of Tumor Cell Escape Following Specific Immunotherapy
Frost, P., & Bonavida, B. (2000) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2000.15.141 · Cited by 5
Research works printed but not linked: 2
- C Qian, J Prieto, Gene therapy of cancer: Induction of antitumor immunity. Cell Mol Immunol 1, 105–111 (2004).
- 10.1562/0031-8655(2001)074<0712:IOSNRI>2.0.CO;2 · DOI
Cited by
Sorted by citations
Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization
Celli, J. P., Spring, B. Q., Rizvi, I., Evans, C. L., Samkoe, K. S., Verma, S., Pogue, B. W., & Hasan, T. G. (2010) · Chemical Reviews · doi:10.1021/cr900300p · Cited by 2,359
Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions
van Straten, D., Mashayekhi, V., de Bruijn, H., Oliveira, S., & Robinson, D. J. (2017) · Cancers · doi:10.3390/cancers9020019 · Cited by 1,042
Cancer nanomedicine for combination cancer immunotherapy
Nam, J., Son, S., Park, K. S., Zou, W., Shea, L. D., & Moon, J. J. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0108-1 · Cited by 955
Howard, A., O’Donoghue, M., Feeney, A., & Sleator, R. D. (2012) · Virulence · doi:10.4161/viru.19700 · Cited by 855
Emerging combination strategies with phototherapy in cancer nanomedicine
Xie, Z., Fan, T., An, J., Choi, W., Duo, Y., Ge, Y., Zhang, B., Nie, G., Xie, N., Zheng, T., et al. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00215a · Cited by 718
Metadata
- Authors
- Castano, A. P., Mroz, P., Wu, M. X., & Hamblin, M. R.
- Affiliations
- *Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114;
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-04-08
- Volume
- 105
- Issue
- 14
- Pages
- 5495-5500
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2291083
- OpenAlex
- W2108157005
- Cited by
- 201
- References
- 58
- Citations by year
- 2025: 4 · 2024: 7 · 2023: 15 · 2022: 12 · 2021: 18 · 2020: 13 · 2019: 17 · 2018: 10 · 2017: 10 · 2016: 7 · 2015: 14 · 2014: 18 · 2013: 8 · 2012: 10
- FWCI
- 11.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA083882)
- National Institute of Allergy and Infectious Diseases (R01AI050875, R01CA/AI838801)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- photodynamic therapy, cyclophosphamide, antitumor immunity, regulatory T cells, verteporfin, benzoporphyrin derivative, reticulum cell sarcoma, J774 cells, cancer immunotherapy, tumor-specific T cells, immunological memory, combination therapy, metastatic cancer
- MeSH terms
- Animals, Cyclophosphamide, Immunity, Neoplasm Metastasis, Neoplasms, Experimental, Photochemotherapy, Survival Rate, Treatment Outcome, Cell Line, Tumor, Tumor Burden, T-Lymphocytes, Regulatory, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review