The status of immunosuppression in patients with stage IIIB or IV non-small-cell lung cancer correlates with the clinical characteristics and response to chemotherapy
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Background: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation via the kynurenine (Kyn) pathway, which inhibits the proliferation of T cells and induces the apoptosis of T cells, leading to immune tolerance. Therefore, IDO has been considered as the most important mechanism for tumor cells to escape from immune response. Previous studies suggested that IDO might be involved in the progression of tumor and resistance to chemotherapy. Several preclinical and clinical studies have proven that IDO inhibitors can regulate IDO-mediated tumor immune escape and potentiate the effect of chemotherapy. Thus, the present study investigated the correlation between the clinical parameters, responses to chemotherapy, and IDO activity to provide a theoretical basis for the clinical application of IDO inhibitors to improve the suppression status and poor prognosis in cancer patients. Methods: The serum concentrations of Trp and Kyn were measured by high-performance liquid chromatography in 252 patients with stage IIIB or IV non-small-cell lung cancer, and 55 healthy controls. The IDO activity was determined by calculating the serum Kyn-to-Trp (Kyn/Trp) ratio. Results: The IDO activity was significantly higher in the lung cancer patients than in the controls (median 0.0389 interquartile range [0.0178–0.0741] vs 0.0111 [0.0091–0.0133], respectively; P <0.0001). In addition, patients with adenocarcinoma had higher IDO activity than patients with nonadenocarcinoma (0.0449 [0.0189–0.0779] vs 0.0245 [0.0155–0.0563], respectively; P =0.006). Furthermore, patients with stage IIIB disease had higher IDO activity than patients with stage IV disease (0.0225 [0.0158–0.0595] vs 0.0445 [0.0190–0.0757], respectively; P =0.012). The most meaningful discovery was that there was a significant difference between the partial response (PR) patients and the stable disease (SD) and progressive disease (PD) patients (0.0240 [0.0155–0.0381] vs 0.0652 [0.0390–0.0831] vs 0.0868 [0.0209–0.0993], respectively, P <0.0001). Conclusion: IDO activity was increased in lung cancer patients. Higher IDO activity correlated with histological types and disease stages of lung cancer patients, induced the cancer cells’ resistance to chemotherapy, and decreased the efficacy of chemotherapy. Keywords: advanced non-small-cell lung cancer, indoleamine 2,3-dioxygenase, immune escape, chemotherapy response, tumor immunotherapy
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NSCLC patients have increased tryptophan catabolism compared with the general population, leading to higher serum kynurenine, which is associated with advanced stage at diagnosis, poor prognosis and chemotherapy resistance.
“Compared with the general population, patients with NSCLC have increased tryptophan catabolism, which leads to higher kynurenine serum concentrations and has been associated with advanced stage disease at diagnosis, an unfavourable prognosis and resistance to chemotherapy148,149.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [149]
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Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
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- Authors
- Wang, Y., Hu, G.-F., & Wang, Z.
- Affiliations
- University of Jinan (CN)
- Shandong University (CN)
- Corresponding author
- Wang, Zhehai
- Venue
- OncoTargets and Therapy
- Publisher
- Informa UK Limited
- Published
- 2017-07
- Volume
- Volume 10
- Pages
- 3557-3566
- ISSN
- 1178-6930 (ISSN-L)
- PMC
- PMC5530847
- OpenAlex
- W2737710038
- Cited by
- 21
- References
- 108
- Citations by year
- 2025: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 2
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- OncoTargets and Therapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- non-small cell lung cancer, indoleamine 2,3-dioxygenase, kynurenine pathway, tryptophan, kynurenine/tryptophan ratio, tumor immune evasion, chemotherapy response, IDO inhibitors, adenocarcinoma, tumor stage, prognostic factors, immunosuppression, T cell apoptosis, immune tolerance
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