ESTRO 2024 - Abstract Book

S5186

Radiobiology - Immuno-radiobiology

ESTRO 2024

Material/Methods:

Using an in-house established humanized mouse model, we monitored tumor growth in bilateral subcutaneous tumor settings in three human tumor models (MM043 melanoma, 786-O renal cell carcinoma and H1650 non small cell lung cancer) under different dose-fractionation regimens of photon irradiation, 1x2Gy, 1x5Gy, 1x10Gy or 3x8Gy (using the last generation SMART+ micro-irradiator) alone or in combination with immune checkpoint inhibition (anti-PD-1 alone or in combination with anti-CTLA-4). Human immune reconstitution was monitored by flow cytometry analysis on mouse peripheral blood along experiments. Tumor immune infiltration and micro environment analyses were performed by flow cytometry, immunohistochemistry, and cytokine array

Results:

Our results show the progressive reconstitution of human immune populations in mouse peripheral blood from the engrafted hCD34+ hematopoietic stem cells. Human CD45+ cells exceed the 25% threshold of all blood leukocytes, confirming their “humanized” status. Monitoring of human immune populations in mice peripheral blood showed the presence of hCD19+ B lymphocytes, CD3+ T lymphocytes (both hCD4+ and hCD8+), hCD14+ monocytes and hCD56+ natural killer cells. Tumor growth was assessed under vehicle or immunotherapy in non humanized versus humanized mice, confirming that the response to immunotherapy relies on the reconstituted human immune system. Anti-tumoral responses were assessed under immunotherapy or radiotherapy alone or the combination thereof, showing a drastic improvement in tumor control upon the addition of radiotherapy to ICIs and modulation of tumor-infiltrating immune populations under the different treatments. These results provide new insights into the benefits of the combination regimens proposed and their immunomodulatory effects.

Conclusion:

We provide a first-time report for the use of radiotherapy in combination with ICIs in a humanized mouse model for cancer treatment and give new insights into the benefits of such combinations.

Keywords: radiotherapy, ICI, Humanized mouse

2662

Proffered Paper

Systemic effects of radiotherapy combined with lenalidomide in mouse solid tumor models

Kateryna Onyshchenko 1,2,3 , Ren Luo 1,4,5 , Xi Rao 1,2,3 , Elke Firat 1 , Gabriele Niedermann 1,2,3

1 University of Freiburg, Department of Radiation Oncology, Faculty of Medicine, Freiburg im Breisgau, Germany. 2 German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg im Breisgau, Germany. 3 German Cancer Research Center, DKFZ, Heidelberg, Germany. 4 West China Hospital, Division of Thoracic Tumor Multimodality Treatment, Cancer Center, Chengdu, Sichuan, China. 5 West China Hospital, Department of Radiation Oncology, Cancer Center, Chengdu, Sichuan, China