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Fractionated radiotherapy with 3 x 8 Gy induces systemic anti-tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response

THPM Habets, T Oth, AW Houben, MJAJ Huijskens, BLMG Senden-Gijsbers, MCA Schnijderberg, Boudewijn Brans UGent, LJ Dubois, P Lambin, M De Saint-Hubert, et al. (2016) PLOS ONE. 11(7).
abstract
Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral antitumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
COLONY-STIMULATING FACTOR, CELL-DEATH, CANCER-IMMUNOTHERAPY, METASTATIC MELANOMA, LOCAL RADIOTHERAPY, EFFECTOR-CELLS, LUNG-CANCER, IN-VIVO, REGRESSION, ANTIBODIES
journal title
PLOS ONE
PLoS One
volume
11
issue
7
article number
e0159515
pages
19 pages
Web of Science type
Article
Web of Science id
000380169300074
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
2.806 (2016)
JCR rank
15/64 (2016)
JCR quartile
1 (2016)
ISSN
1932-6203
DOI
10.1371/journal.pone.0159515
language
English
UGent publication?
no
classification
A1
id
8510164
handle
http://hdl.handle.net/1854/LU-8510164
date created
2017-02-20 10:11:11
date last changed
2017-10-05 11:21:50
@article{8510164,
  abstract     = {Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral antitumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects.},
  articleno    = {e0159515},
  author       = {Habets, THPM and Oth, T and Houben, AW and Huijskens, MJAJ and Senden-Gijsbers, BLMG and Schnijderberg, MCA and Brans, Boudewijn and Dubois, LJ and Lambin, P and De Saint-Hubert, M and Germeraad, WTV and Tilanus, MGJ and Mottaghy, FM and Bos, GMJ and Vanderlocht, J},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {COLONY-STIMULATING FACTOR,CELL-DEATH,CANCER-IMMUNOTHERAPY,METASTATIC MELANOMA,LOCAL RADIOTHERAPY,EFFECTOR-CELLS,LUNG-CANCER,IN-VIVO,REGRESSION,ANTIBODIES},
  language     = {eng},
  number       = {7},
  pages        = {19},
  title        = {Fractionated radiotherapy with 3 x 8 Gy induces systemic anti-tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response},
  url          = {http://dx.doi.org/10.1371/journal.pone.0159515},
  volume       = {11},
  year         = {2016},
}

Chicago
Habets, THPM, T Oth, AW Houben, MJAJ Huijskens, BLMG Senden-Gijsbers, MCA Schnijderberg, Boudewijn Brans, et al. 2016. “Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-tumour Responses and Abscopal Tumour Inhibition Without Modulating the Humoral Anti-tumour Response.” Plos One 11 (7).
APA
Habets, T., Oth, T., Houben, A., Huijskens, M., Senden-Gijsbers, B., Schnijderberg, M., Brans, B., et al. (2016). Fractionated radiotherapy with 3 x 8 Gy induces systemic anti-tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response. PLOS ONE, 11(7).
Vancouver
1.
Habets T, Oth T, Houben A, Huijskens M, Senden-Gijsbers B, Schnijderberg M, et al. Fractionated radiotherapy with 3 x 8 Gy induces systemic anti-tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response. PLOS ONE. 2016;11(7).
MLA
Habets, THPM, T Oth, AW Houben, et al. “Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-tumour Responses and Abscopal Tumour Inhibition Without Modulating the Humoral Anti-tumour Response.” PLOS ONE 11.7 (2016): n. pag. Print.