American Association for Cancer Research
10780432ccr170438-sup-179042_2_supp_4060767_4qtsjn.pptx (71.54 kB)

Figure S1 from In Situ Vaccination after Accelerated Hypofractionated Radiation and Surgery in a Mesothelioma Mouse Model

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posted on 2023-03-31, 20:25 authored by Luis De La Maza, Matthew Wu, Licun Wu, Hana Yun, Yidan Zhao, Mark Cattral, Andrea McCart, BC John Cho, Marc de Perrot

The AE17 and AB12 cell lines do not express PD-L1



Purpose: How best to sequence and integrate immunotherapy into standard of care is currently unknown. Clinical protocols with accelerated nonablative hypofractionated radiation followed by surgery could provide an opportunity to implement immune checkpoint blockade.Experimental Design: We therefore assessed the impact of nonablative hypofractionated radiation on the immune system in combination with surgery in a mouse mesothelioma model. Blunt surgery (R1 resection) was used to analyze the short-term effect, and radical surgery (R0 resection) was used to analyze the long-term effect of this radiation protocol before surgery.Results: Nonablative hypofractionated radiation led to a specific immune activation against the tumor associated with significant upregulation of CD8+ T cells, limiting the negative effect of an incomplete resection. The same radiation protocol performed 7 days before radical surgery led to a long-term antitumor immune protection that was primarily driven by CD4+ T cells. Radical surgery alone or with a short course of nonablative radiation completed 24 hours before radical surgery did not provide this vaccination effect. Combining this radiation protocol with CTLA-4 blockade provided better results than radiation alone. The effect of PD-1 or PD-L1 blockade with this radiation protocol was less effective than the combination with CTLA-4 blockade.Conclusions: A specific activation of the immune system against the tumor contributes to the benefit of accelerated, hypofractionated radiation before surgery. Nonablative hypofractionated radiation combined with surgery provides an opportunity to introduce immune checkpoint blockades in the clinical setting. Clin Cancer Res; 23(18); 5502–13. ©2017 AACR.

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