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From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Results of in vitro clonogenic survival assays with increasing radiation doses. A, Human papillomavirus–positive (HPV+) human
tumor cells (UMSCC-47 and UPCI-SCC90) are more resistant to radiation than are HPV-negative (HPV−) cells (UMSCC-1, -19, and
-84). Cells were irradiated with the indicated dose, and percentage survival was calculated by comparing the number of surviving
colonies with the number of cells plated (3 plates per group; the results were averaged across 2 experiments). B, The HPV+ mouse
tonsil epithelial cells are more resistant than theCopyright
HPV− cells.
Colony-forming
assay of cells was performed as described in Figure
© 2009
American Medical
Date
of download:
5/11/2017
1A. Error
bars represent
SE.
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From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Radiation-related clearance of human papillomavirus–positive (HPV+) tumors in mice is enhanced by an intact immune response.
Tumor growth curves and survival curves are shown for wild-type C57BL/6 mice (A and B) and C57BL/6 B6.129S7-Rag1tm1Mom/J
(RAG-1) mice (C and D) implanted with HPV+ or HPV negative (HPV−) mouse tonsil epithelial cells. Six mice were used in each
group. Tumors were locally irradiated with the indicated amount of radiation 7 days after implantation (XRT). Results of the log-rank
test, with α = .01, show that survival of wild-typeCopyright
mice vs RAG-1
mice implanted
© 2009 American
Medicalwith HPV+ tumors is significant at 0 Gy (P = .002),
Date
5/11/2017
8 Gy of
(Pdownload:
= .007), 16
Gy (P = .006), and 24 Gy (P =Association.
.003) but did
not
reach
significance at 32 Gy (P = .03) due to 1 RAG-1 mouse
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with tumor clearance. The difference in survival between wild-type mice implanted with HPV+ vs HPV− tumors was significant at 32
From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Growth inhibition of bulky human papillomavirus–positive (HPV+) tumors is enhanced by vaccination with an adenovirus expressing
HPV-16 E6 and E7 oncogenes (Ad-E6/E7). The C57BL/6 mice were injected with HPV+ mouse tonsil epithelial cells, and tumors
were allowed to grow to 1 cm. Mice were vaccinated with either control (AdEmpty) or Ad-E6/E7 on day 14 after tumor implantation.
To determine whether timing of vaccination alters response, a separate group of mice was also vaccinated with Ad-E6/E7 21 days
after implantation. Six mice were used in each treatment
flanks
were locally irradiated with 20 Gy of radiation (XRT) on
Copyright group.
© 2009 Mice
American
Medical
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day 28
after tumor5/11/2017
implantation. Growth curves (A)Association.
and survival
curves
(B)
for
All rights reserved.the various groups show a slight improvement in
survival (P = .003, log-rank test, with α = .01) for the mice receiving vaccination with Ad-E6/E7 14 days before radiation therapy.
From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Human papillomavirus–positive (HPV+) mouse tonsil epithelial cells (MTECs) are more resistant to cisplatin than are HPV-negative
(HPV−) HPV− MTECs. The MTECs were plated, were allowed to attach, and were treated with cisplatin for 24 hours; colony
formation was then assessed. The HPV+ and HPV− MTECs were incubated with escalating doses of cisplatin and were allowed to
grow until a 15-cell colony size was achieved. Three plates were used per condition, and the results were averaged across 2
experiments. The percentage of surviving cells that
formed
colonies
were quantified.
The HPV+ MTECs are more resistant
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© 2009
American
Medical
Date
of download:
5/11/2017
(approximately
63%)
to cisplatin than are the HPV−
cells
(P
<
.02,
Mann-Whitney
test).
Error bars represent SE.
Association. All rights reserved.
From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Human papillomavirus–positive (HPV+) tumors are more sensitive to treatment with cisplatin than are HPV-negative (HPV−) tumors
in immune-competent mice. Tumor growth rates and survival rates were quantified after the indicated doses of cisplatin in C57BL/6
mice (A and B) C57BL/6 and B6.129S7-Rag1tm1Mom/J (RAG-1) mice (C). Six mice were used in each group. Mice received 3 weekly
intraperitoneal injections of cisplatin, with the first dose starting 1 week after tumor implantation with 1 × 106 HPV+ or HPV− mouse
tonsil epithelial cells. Difference in survival for HPV+
tumors
comparing
wild-type
Copyright
© 2009
American
Medical vs RAG-1 mice and the difference in survival for
2 doses (P < .01, log-rank test, with α = .01). Error bars
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5/11/2017
HPV+ofvs
HPV− tumors
in wild-type mice was different
at
10and
20-mg/m
Association. All rights reserved.
represent SE.
From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Cisplatin response can be partially restored by adoptive transfer of splenocytes into B6.129S7-Rag1tm1Mom/J (RAG-1) mice. Immune
cells from wild-type C57BL/6 mice were adoptively transferred into C57BL/6 RAG-1 mice, human papillomavirus–positive mouse
tonsil epithelial cells were implanted, and response to weekly cisplatin was compared with that of naive RAG-1 mice (6 mice per
group). Mice receiving adoptive transfer had slower tumor growth and greater partial response than did control RAG-1 mice.
Treatment with cisplatin, 20 mg/m2 every week for
3 weeks,
was American
initiated 1Medical
week after tumor cell implantation (cisplatin treatment).
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© 2009
Date
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5/11/2017
Errorofbars
represent
SE.
Association. All rights reserved.
From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Cisplatin response is insufficient to induce clearance of bulky tumors. To compare the response for bulky vs small tumor burdens,
C57BL/6 mice were implanted with human papillomavirus–positive mouse tonsil epithelial cells and were treated with cisplatin, 20
mg/m2 (3 weekly doses), either 7 or 21 days (approximately 1 cm in greatest dimension) after implantation (6 mice per group).
Cisplatin treatment of bulky tumors slowed tumor growth but was not sufficient to result in complete remission when tumors were
larger. The difference in survival between treatment
at day© 72009
andAmerican
day 21 was
significant (P = .007, log-rank test, with α = .01).
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Medical
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Association. All rights reserved.
From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Clonogenic survival of human papillomavirus–positive (HPV+) and HPV-negative (HPV−) mouse tonsil epithelial cells treated with
concurrent radiation and cisplatin in vitro. The cells were split 24 hours after treatment with the indicated doses of radiation and 0.25
μg/mL of cisplatin, and colonies greater than 15 cells were counted at 14 days. Three plates were used per condition, with results
averaged from 2 experiments. Surviving fractions of cells were compared with initial numbers of plated cells. No difference was seen
in sensitivity to combined radiation and cisplatinCopyright
use between
HPV+
and HPV−
mouse tonsil epithelial cells. Error bars represent
© 2009
American
Medical
Date
SE. of download: 5/11/2017
Association. All rights reserved.
From: Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head
and Neck Cancer
Arch Otolaryngol Head Neck Surg. 2009;135(11):1137-1146. doi:10.1001/archoto.2009.159
Figure Legend:
Cisplatin and radiation responses in vivo with and without the adenovirus-expressing human papillomavirus (HPV) 16 E6 and E7
oncogene (Ad-E6/E7) vaccination. A, In vivo response of bulky tumors either untreated (RAG-1 and wild type, no treatment) or
treated with 3 doses of concurrent radiation (8 Gy weekly) and cisplatin (3 doses of 20 mg/m 2 weekly) implanted in either wild-type
C57BL/6 or C57BL/6 RAG-1 mice (the other 4 groups). The HPV-positive (HPV+) cells were injected in C57BL/6 or C57BL/6 RAG-1
mice and were allowed to grow for 14 days (6 mice
per group).
the treatment
groups, mice were divided again to be vaccinated
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© 2009InAmerican
Medical
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with either
control 5/11/2017
AdEmpty or Ad-E6/E7 14 days after
tumor
implantation
(adenovirus
treatment). Cisplatin and radiation
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administration in the treatment groups began on day 21 after implantation of tumor cells. Growth curves (A) and survival curves (B)