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Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer
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) pat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Landes Bioscience
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661168/ https://www.ncbi.nlm.nih.gov/pubmed/23802083 http://dx.doi.org/10.4161/onci.23428 |
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author | Creelan, Ben C. Antonia, Scott Bepler, Gerold Garrett, Timothy J. Simon, George R. Soliman, Hatem H. |
author_facet | Creelan, Ben C. Antonia, Scott Bepler, Gerold Garrett, Timothy J. Simon, George R. Soliman, Hatem H. |
author_sort | Creelan, Ben C. |
collection | PubMed |
description | 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. The mean plasma Kyn/Trp ratio was used as a surrogate indicator of IDO activity. The 33 participants were distributed as follows: 15 females, 18 males; median age = 62; median overall survival (OS) = 22.4 (95% CI 19.3–25.1) months; median progression-free survival (PFS) = 11.5 (95% CI 6.7–16.3) months. The mean Kyn/Trp ratio at baseline (4.5 ± 2.8) was higher than that of healthy controls (2.9 ± 1.9, p = 0.03) and increased after induction therapy (5.2 ± 3.2, p = 0.08) and chemoradiation (5.8 ± 3.9, p = 0.01). The post-treatment Kyn/Trp ratio and radiologic responses were not significantly associated at any time point. 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. |
format | Online Article Text |
id | pubmed-3661168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Landes Bioscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-36611682013-06-25 Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer Creelan, Ben C. Antonia, Scott Bepler, Gerold Garrett, Timothy J. Simon, George R. Soliman, Hatem H. Oncoimmunology Original Research 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. The mean plasma Kyn/Trp ratio was used as a surrogate indicator of IDO activity. The 33 participants were distributed as follows: 15 females, 18 males; median age = 62; median overall survival (OS) = 22.4 (95% CI 19.3–25.1) months; median progression-free survival (PFS) = 11.5 (95% CI 6.7–16.3) months. The mean Kyn/Trp ratio at baseline (4.5 ± 2.8) was higher than that of healthy controls (2.9 ± 1.9, p = 0.03) and increased after induction therapy (5.2 ± 3.2, p = 0.08) and chemoradiation (5.8 ± 3.9, p = 0.01). The post-treatment Kyn/Trp ratio and radiologic responses were not significantly associated at any time point. 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. Landes Bioscience 2013-03-01 2013-03-01 /pmc/articles/PMC3661168/ /pubmed/23802083 http://dx.doi.org/10.4161/onci.23428 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Original Research Creelan, Ben C. Antonia, Scott Bepler, Gerold Garrett, Timothy J. Simon, George R. Soliman, Hatem H. Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer |
title | Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer |
title_full | Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer |
title_fullStr | Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer |
title_full_unstemmed | Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer |
title_short | Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer |
title_sort | indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in stage iii non-small cell lung cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661168/ https://www.ncbi.nlm.nih.gov/pubmed/23802083 http://dx.doi.org/10.4161/onci.23428 |
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