Assessing the effects of Concurrent versus sequential cisplatin/radiotherapy on immune status in lung tumor-bearing C57BL/6 mice

Chiao Jung Kao, Gregory T. Wurz, Yi Chen Lin, Daniel P. Vang, Stephen M Griffey, Michael Wolf, Michael W. Degregorio

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Concurrent and sequential cisplatin-based chemoradiotherapy regimens are standard therapeutic approaches in cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect antigen-specific immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential cisplatin/radiotherapy on immune status in a lung cancer mouse model. A total of 150 C57BL/6 mice were randomized into six treatment groups: control; 8 Gy thoracic radiotherapy (dose schedules 1 and 2); cisplatin 2.5 mg/kg i.p.; cisplatin + radiotherapy (concurrent); and cisplatin + radiotherapy (sequential; n = 25, all groups). At the end of the study (week 41), serum cytokines were assessed by multiplex immunoassay, surface markers of spleen-derived lymphocytes were assessed by immunostaining and flow cytometry, lung tumor expression of programmed death ligands 1 and 2 (PD-L1/2) was evaluated by immunohistochemistry, and miRNA profiling was performed in serum and lymphocytes by quantitative real-time PCR. Lung whole mounts were prepared to assess treatment effects on lung tumor foci formation. The results showed that sequential chemoradiotherapy (two cycles of cisplatin followed by 8 Gy radiotherapy) had equivalent antitumor activity as concurrent therapy. However, sequential cisplatin/radiotherapy resulted in significant differences in several immune response biomarkers, including regulatory T cells, miR-29c, expression of costimulatory molecule CD28, and serum IFNγ. PD-L1 and PD-L2 were strongly expressed in tumor foci, but no trend was seen between groups. These results suggest that monitoring immune status may be necessary when designing treatment regimens combining immunotherapy with chemoradiotherapy.

Original languageEnglish (US)
Pages (from-to)741-750
Number of pages10
JournalCancer immunology research
Volume3
Issue number7
DOIs
StatePublished - Jul 1 2015

Fingerprint

Inbred C57BL Mouse
Cisplatin
Radiotherapy
Lung
Chemoradiotherapy
Neoplasms
Immunotherapy
Appointments and Schedules
Therapeutics
Serum
Lymphocytes
Immunologic Monitoring
Regulatory T-Lymphocytes
MicroRNAs
Immunoassay
Real-Time Polymerase Chain Reaction
Lung Neoplasms
Flow Cytometry
Thorax
Spleen

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Medicine(all)

Cite this

Assessing the effects of Concurrent versus sequential cisplatin/radiotherapy on immune status in lung tumor-bearing C57BL/6 mice. / Kao, Chiao Jung; Wurz, Gregory T.; Lin, Yi Chen; Vang, Daniel P.; Griffey, Stephen M; Wolf, Michael; Degregorio, Michael W.

In: Cancer immunology research, Vol. 3, No. 7, 01.07.2015, p. 741-750.

Research output: Contribution to journalArticle

Kao, Chiao Jung ; Wurz, Gregory T. ; Lin, Yi Chen ; Vang, Daniel P. ; Griffey, Stephen M ; Wolf, Michael ; Degregorio, Michael W. / Assessing the effects of Concurrent versus sequential cisplatin/radiotherapy on immune status in lung tumor-bearing C57BL/6 mice. In: Cancer immunology research. 2015 ; Vol. 3, No. 7. pp. 741-750.
@article{15c70ba3d6794f7485d0898ebe62c58a,
title = "Assessing the effects of Concurrent versus sequential cisplatin/radiotherapy on immune status in lung tumor-bearing C57BL/6 mice",
abstract = "Concurrent and sequential cisplatin-based chemoradiotherapy regimens are standard therapeutic approaches in cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect antigen-specific immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential cisplatin/radiotherapy on immune status in a lung cancer mouse model. A total of 150 C57BL/6 mice were randomized into six treatment groups: control; 8 Gy thoracic radiotherapy (dose schedules 1 and 2); cisplatin 2.5 mg/kg i.p.; cisplatin + radiotherapy (concurrent); and cisplatin + radiotherapy (sequential; n = 25, all groups). At the end of the study (week 41), serum cytokines were assessed by multiplex immunoassay, surface markers of spleen-derived lymphocytes were assessed by immunostaining and flow cytometry, lung tumor expression of programmed death ligands 1 and 2 (PD-L1/2) was evaluated by immunohistochemistry, and miRNA profiling was performed in serum and lymphocytes by quantitative real-time PCR. Lung whole mounts were prepared to assess treatment effects on lung tumor foci formation. The results showed that sequential chemoradiotherapy (two cycles of cisplatin followed by 8 Gy radiotherapy) had equivalent antitumor activity as concurrent therapy. However, sequential cisplatin/radiotherapy resulted in significant differences in several immune response biomarkers, including regulatory T cells, miR-29c, expression of costimulatory molecule CD28, and serum IFNγ. PD-L1 and PD-L2 were strongly expressed in tumor foci, but no trend was seen between groups. These results suggest that monitoring immune status may be necessary when designing treatment regimens combining immunotherapy with chemoradiotherapy.",
author = "Kao, {Chiao Jung} and Wurz, {Gregory T.} and Lin, {Yi Chen} and Vang, {Daniel P.} and Griffey, {Stephen M} and Michael Wolf and Degregorio, {Michael W.}",
year = "2015",
month = "7",
day = "1",
doi = "10.1158/2326-6066.CIR-14-0234",
language = "English (US)",
volume = "3",
pages = "741--750",
journal = "Cancer immunology research",
issn = "2326-6066",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Assessing the effects of Concurrent versus sequential cisplatin/radiotherapy on immune status in lung tumor-bearing C57BL/6 mice

AU - Kao, Chiao Jung

AU - Wurz, Gregory T.

AU - Lin, Yi Chen

AU - Vang, Daniel P.

AU - Griffey, Stephen M

AU - Wolf, Michael

AU - Degregorio, Michael W.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Concurrent and sequential cisplatin-based chemoradiotherapy regimens are standard therapeutic approaches in cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect antigen-specific immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential cisplatin/radiotherapy on immune status in a lung cancer mouse model. A total of 150 C57BL/6 mice were randomized into six treatment groups: control; 8 Gy thoracic radiotherapy (dose schedules 1 and 2); cisplatin 2.5 mg/kg i.p.; cisplatin + radiotherapy (concurrent); and cisplatin + radiotherapy (sequential; n = 25, all groups). At the end of the study (week 41), serum cytokines were assessed by multiplex immunoassay, surface markers of spleen-derived lymphocytes were assessed by immunostaining and flow cytometry, lung tumor expression of programmed death ligands 1 and 2 (PD-L1/2) was evaluated by immunohistochemistry, and miRNA profiling was performed in serum and lymphocytes by quantitative real-time PCR. Lung whole mounts were prepared to assess treatment effects on lung tumor foci formation. The results showed that sequential chemoradiotherapy (two cycles of cisplatin followed by 8 Gy radiotherapy) had equivalent antitumor activity as concurrent therapy. However, sequential cisplatin/radiotherapy resulted in significant differences in several immune response biomarkers, including regulatory T cells, miR-29c, expression of costimulatory molecule CD28, and serum IFNγ. PD-L1 and PD-L2 were strongly expressed in tumor foci, but no trend was seen between groups. These results suggest that monitoring immune status may be necessary when designing treatment regimens combining immunotherapy with chemoradiotherapy.

AB - Concurrent and sequential cisplatin-based chemoradiotherapy regimens are standard therapeutic approaches in cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect antigen-specific immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential cisplatin/radiotherapy on immune status in a lung cancer mouse model. A total of 150 C57BL/6 mice were randomized into six treatment groups: control; 8 Gy thoracic radiotherapy (dose schedules 1 and 2); cisplatin 2.5 mg/kg i.p.; cisplatin + radiotherapy (concurrent); and cisplatin + radiotherapy (sequential; n = 25, all groups). At the end of the study (week 41), serum cytokines were assessed by multiplex immunoassay, surface markers of spleen-derived lymphocytes were assessed by immunostaining and flow cytometry, lung tumor expression of programmed death ligands 1 and 2 (PD-L1/2) was evaluated by immunohistochemistry, and miRNA profiling was performed in serum and lymphocytes by quantitative real-time PCR. Lung whole mounts were prepared to assess treatment effects on lung tumor foci formation. The results showed that sequential chemoradiotherapy (two cycles of cisplatin followed by 8 Gy radiotherapy) had equivalent antitumor activity as concurrent therapy. However, sequential cisplatin/radiotherapy resulted in significant differences in several immune response biomarkers, including regulatory T cells, miR-29c, expression of costimulatory molecule CD28, and serum IFNγ. PD-L1 and PD-L2 were strongly expressed in tumor foci, but no trend was seen between groups. These results suggest that monitoring immune status may be necessary when designing treatment regimens combining immunotherapy with chemoradiotherapy.

UR - http://www.scopus.com/inward/record.url?scp=84962040767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962040767&partnerID=8YFLogxK

U2 - 10.1158/2326-6066.CIR-14-0234

DO - 10.1158/2326-6066.CIR-14-0234

M3 - Article

C2 - 25672395

AN - SCOPUS:84962040767

VL - 3

SP - 741

EP - 750

JO - Cancer immunology research

JF - Cancer immunology research

SN - 2326-6066

IS - 7

ER -