IDO Immune Status After Radiotherapy in Patients With IV Stage Non-Small Cell Lung Cancer: An Exploratory Study

Abstract

<h3>Purpose/Objective(s)</h3> Host immunity has a significant impact on radiotherapy (RT) outcomes in cancer. We have previously demonstrated that Indoleamine 2, 3-dioxygenase (IDO), a known immunoinhibitory kinase, predicts the survival of patients with stage I/II after RT alone and stage III non-small cell lung cancer (NSCLC) after chemoradiation. We hypothesize that the IDO activity levels in the blood also change in patients with stage IV NSCLC following radiotherapy. <h3>Materials/Methods</h3> This was part of a prospective study of circulating immune biomarkers for prognosis and prediction. Newly diagnosed or recurrent stage IV NSCLC patients were eligible. Blood samples were obtained before and after RT start and platelet-poor plasma samples were used for the kynurenine (Kyn) and tryptophan (Trp) measurement by high-performance liquid chromatography. Kyn and Trp was detected on a UV/vis channel at 360 nm and 285 nm, respectively, with more than 95% re-productivity. IDO activity was defined as the ratio between Kyn and Trp in synchronization. Student T-test was applied for group comparison. Data are presented as mean and 95% confidence interval (CI). <i>P</i> value < 0.05 was considered as statistical significance. <h3>Results</h3> Between July 2019 and Dec 2020, a total of 54 patients with stage IV NSCLC treated with radiotherapy was recruited. RT dose ranged from 20-60 Gray in 5-30 fractions, covering thoracic, spines or brain. Higher concentration of Kyn (mean = 1.88, CI = 1.48-2.27 mM) was detected before RT, compared with the Kyn concentration (mean = 1.20, CI = 0.70-1.70 mM) after RT (<i>P</i> = 0.052). The mean concentration of Trp was 20.81 (CI = 17.01-24.62) mM before RT, compared with 19.01 (CI = 17.03-21.00) mM after RT with no significant change (<i>P</i> = 0.982). In addition, the IDO activity (mean = 0.11, CI = 0.08-0.14) before RT was higher than the IDO activity after RT (mean = 0.08, CI = 0.05-0.10) with <i>P</i> = 0.130. Furthermore, a subgroup analysis of the IDO activity in patients with distant metastasis (n = 31) was conducted. The mean concentration of Kyn was significantly decreased from 1.78 (CI = 1.67-2.67) mM before RT to 0.68 (CI = 0.28-2.09) mM after RT (<i>P</i> = 0.028). The mean concentration of Trp was 18.12 (CI = 15.39-20.84) mM before RT versus 18.64 (CI = 14.41-22.86) mM after RT (<i>P</i> = 0.847). Besides, the IDO activity was also reduced from 0.15 (CI = 0.09-0.20) before RT to 0.07 (CI = 0.01-0.13) after RT (<i>P</i> = 0.051). <h3>Conclusion</h3> This study reveals that the plasma kynurenine and IDO activity is reduced after RT, suggesting that potential roles of RT in releasing immune suppression status of the host that can be simply tested by IDO activity in patients with stage IV NSCLC.