An antitumor immune response is evoked by partial-volume single-dose radiation in 2 murine models Journal Article


Authors: Markovsky, E.; Budhu, S.; Samstein, R. M.; Li, H.; Russell, J.; Zhang, Z.; Drill, E.; Bodden, C.; Chen, Q.; Powell, S. N.; Merghoub, T.; Wolchok, J. D.; Humm, J.; Deasy, J. O.; Haimovitz-Friedman, A.
Article Title: An antitumor immune response is evoked by partial-volume single-dose radiation in 2 murine models
Abstract: Purpose: This study examined tumor growth delay resulting from partial irradiation in preclinical mouse models. Methods and Materials: We investigated 67NR murine orthotopic breast tumors in both immunocompetent and nude mice. Treatment was delivered to 50% or 100% of the tumor using a 2 × 2 cm collimator on a microirradiator. Radiation response was modulated by treatment with anti-CD8 and anti—intercellular adhesion molecule (anti-ICAM) antibodies. Similar experiments were performed using the less immunogenic Lewis lung carcinoma mouse model. Tumor growth delay and γ-H2AX phosphorylation were measured, and immune response was assessed by immunofluorescence and flow cytometry at 1 and 7 days after radiation therapy. Tumor expression of cellular adhesion molecules was also measured at different times after radiation therapy. Results: Partial irradiation led to tumor responses similar to those of fully exposed tumors in immunocompetent mice, but not in nude mice. After a single dose of 10 Gy, infiltration of CD8+ T cells was observed along with increased expression of ICAM. The response to 10 Gy in hemi-irradiated tumors was abrogated by treatment with either anti-CD8 or anti-ICAM antibodies. Similar responses were obtained in the less immunogenic Lewis lung carcinoma mouse model delivering 15 Gy to half the tumor volume. Treatment with FTY720, a compound that inhibits T-cell egress from lymph nodes, did not affect tumor response at the time of CD8+ T cells infiltration in the nonirradiated area of the tumor. This result indicated that the most likely source of these cells is the irradiated portion of the hemi-irradiated tumors. In addition, a significant abscopal effect was observed after partial irradiation with a single dose of 10 Gy in the 67NR model. Conclusions: In these models, radiation controls tumor growth both directly through cell killing and indirectly through immune activation. This outcome raises the possibility that this effect could be induced in the clinic. © 2018 Elsevier Inc.
Keywords: immune system; radiation; radiotherapy; radiation response; tumors; irradiation; antibodies; mammals; cell adhesion; biological organs; t-cells; molecules; adhesion; immune activation; methods and materials; anti-tumor immune; cellular adhesion molecules; intercellular adhesion molecules; lewis lung carcinomata; radiation controls
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 103
Issue: 3
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2019-01-01
Start Page: 697
End Page: 708
Language: English
DOI: 10.1016/j.ijrobp.2018.10.009
PROVIDER: scopus
PUBMED: 30342090
DOI/URL:
Notes: Article -- Export Date: 1 February 2019 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Zhigang Zhang
    237 Zhang
  2. Simon Nicholas Powell
    163 Powell
  3. Jedd D Wolchok
    607 Wolchok
  4. Taha Merghoub
    169 Merghoub
  5. John Laurence Humm
    337 Humm
  6. James Russell
    28 Russell
  7. Joseph Owen Deasy
    276 Deasy
  8. Sadna Budhu
    22 Budhu
  9. Esther Naomi Drill
    24 Drill
  10. Hongyan   Li
    5 Li
  11. Qing Chen
    18 Chen
  12. Chloe Bodden
    1 Bodden