Abstract 3671: Anti-PD-1 treatment may potentiate the radiation-induced lung injury

Abstract

Abstract Purpose: Combination of radiation therapy and anti-PD1 immunotherapy has been investigated both in the lab and in the clinic. Pneumonitis is a rare but potentially fatal toxicity of ant-programmed death-1 (PD-1) monoclonal antibodies (mAbs). The purpose of our study is to address whether anti-PD-1 mAbs will potentiate radiation-induced lung toxicity and mortality in a murine model using Small Animal Radiation Research Platform (SARRP) for lung-targeting irradiation (IR). Methods: Both lungs of male C57bl/6 mice were targeted for 20Gy using the SARRP. Mice were stratified into 4 treatment groups receiving IgG, anti-PD1, IR + IgG, or IR + anti-PD1. IgG or anti-PD-1 mAbs administrated via i.p. injection, with a dosage of 10mg/kg, twice per week for five doses. Acute lung injury was assessed by H&E staining and flow cytometry to measure CD4 or CD8 positive T lymphocytes. A duplicate study (n=10) was performed to determine long-term survival following lung irradiation. Results: 30 days following lung irradiation, lung tissues exhibited abnormal alveoli, with exudates and inflammatory cells in the alveolar septa (H&E staining). The extent of these changes was more prominent in IR+anti-PD-1 group. Moreover, there were significantly (2.1 fold increase; p<0.05) more CD8+ cytotoxic T lymphocytes, rather than CD4+ cells lymphocytes, in the irradiated lung tissues in the group of IR+anti-PD1 compared to that of IR+IgG. Up to 120 days post IR, 90% mice survived in the group of IR+IgG while 70% mice survived in the IR+anti-PD-1 group (p=0.657). Conclusions: Anti-PD-1 mAbs potentiates the radiation-induced pneumonitis, likely mediated by increased CD8+ cytotoxic T lymphocytes. Anti-PD-1 mAbs may increase the radiation-related mortality although it was not statistically significance at the day 120 following IR. Care should be taken for excessive lung toxicities in ongoing clinical trials of combining thoracic RT and anti-PD1 therapy. We will collaborate with NRG to further investigate clinical lung toxicities from combining thoracic radiotherapy with Nivo in the ongoing RTOG 3505 though analyzing the collected biospecimens. Note: This abstract was not presented at the meeting. Citation Format: Jianxin Xue, Shisuo Du, You Lu, Adam Dicker, Bo Lu. Anti-PD-1 treatment may potentiate the radiation-induced lung injury [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3671. doi:10.1158/1538-7445.AM2017-3671