Olink proteomics analysis to identify biomarkers of radiation- and immunotherapy-induced pneumonitis.

Abstract

e20604 Background: Lung cancer remained one of the cancers with the highest incidence and mortality globally. Although the combination of radiation therapy and immunotherapy had shown synergistic effects in efficacy, it also led to severe toxicities such as pneumonitis. However, the limited evidence in the real world demanded a more in-depth investigation into the incidence and mechanisms of pneumonitis. This study aimed to analyze the incidence of radiation and immunotherapy-induced pneumonitis in the real world and utilized Olink proteomics technology to explore potential biomarkers for treatment-related pneumonitis in NSCLC patient. Methods: This study analyzed baseline data from 539 NSCLC patients treated with radiation, immunotherapy, or both between June 2020 and December 2022. We assessed the risk of pneumonitis using multivariate logistic regression and constructed ROC curves to evaluate the predictive value of GTV and lung dosimetric parameters for pneumonitis occurrence. Peripheral blood plasma samples from 12 patients were analyzed using Olink proteomics to identify biomarkers of treatment-related pneumonitis, followed by ELISA validation. Peripheral monocyte counts were monitored to explore their correlation with pneumonitis onset. Results: Combined thoracic radiation and immunotherapy significantly increase the risk of pneumonitis in NSCLC patients. However, clinical factors and radiation dosimetric parameters proved ineffective in predicting the occurrence of treatment-related pneumonitis. Olink Proteomic technology highlighted the critical role of monocyte/macrophages associated factors in the development of clinical treatment-related pneumonitis, particularly MCP-1, CCL19, CXCL5, and CXCL9. Consequently, we hypothesized that peripheral monocytes undergo significant changes in patients with treatment-related pneumonitis, a hypothesis supported by observed increases in peripheral monocyte counts in these patients. Conclusions: Our study found that clinical factors and radiation dosimetric parameters were not effective predictors of radiation and immunotherapy-related pneumonitis. Monocytes/macrophages might play a potential role in the development of pneumonitis. Furthermore, an elevation in peripheral monocyte counts in patients might indicate the occurrence of treatment-related pneumonitis.