Oncoimmunology
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Indoleamine 2,3-dioxygenase (IDO) has recently been proposed to account for tumor-induced immunosuppression by influencing the conversion of tryptophan (Trp) into kynurenine (Kyn). The objective of our study was to correlate IDO activity with disease outcome in non-small cell lung cancer (NSCLC) patients treated with multimodal combination therapy. In a single-arm Phase II trial involving induction gemcitabine and carboplatin followed by concurrent paclitaxel, carboplatin and 74 Gy thoracic radiation in stage III NSCLC patients, plasma was drawn at baseline, post-induction, and post-concurrent therapy. ⋯ No significant correlation was found between baseline Kyn/Trp ratios and OS (HR = 1.1, 95% CI 0.45-2.5) or PFS (HR = 0.74, 95% CI 0.30-1.82). A post-induction chemotherapy increase in IDO activity portended worse OS (HR = 0.43, 95% CI 0.19-0.95, p = 0.037) and PFS (HR = 0.47, 95% CI 0.22-1.0, p = 0.055). This observed increase in IDO transcription may be a means for tumors to evade immunosurveillance.