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. 2018 Aug 6;16(1):219.
doi: 10.1186/s12967-018-1595-3.

Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?

Andrea Botticelli  1 , Bruna Cerbelli  2 , Luana Lionetto  3 , Ilaria Zizzari  4 , Massimiliano Salati  5 , Annalinda Pisano  2 , Mazzuca Federica  6 , Maurizio Simmaco  7 , Marianna Nuti  4 , Paolo Marchetti  6
Affiliations

Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?

Andrea Botticelli et al. J Transl Med. .

Abstract

Background: Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival VSports手机版. Unfortunately, only 25-30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment. .

Methods: Pre-treatment serum concentrations of tryptophan (trp) and kynurenine (kyn) were measured by high-performance liquid chromatography tandem mass spectrometry in NSCLC patients treated with second-line nivolumab V体育安卓版. The IDO activity was expressed with kyn/trp ratio. The associations between kyn/trp ratio and early progression, performance status (PS), age, sex, brain metastases, pleural effusion, progression free survival (PFS) and overall survival (OS) were analyzed using Spearman test and Mann-Whitney test. .

Results: Twenty-six NSCLC patients were included in our study; 14 of them (54%) presented early progression (< 3 months) to nivolumab treatment. The median value of kyn/trp ratio was 0. 06 µg/ml and the median value of quinolinic acid was 68. 45 ng/ml. A significant correlation between early progression and higher kyn/trp ratio and quinolinic acid concentration was observed (p = 0. 017 and p = 0 V体育ios版. 005, respectively). Patients presenting lower values of kyn/trp ratio and quinolinic acid levels showed longer PFS (median PFS not reached versus 3 months; HR: 0. 3; p = 0. 018) and OS (median OS not reached vs 3 months; HR: 0. 18; p = 0. 0005). .

Conclusion: IDO activity, expressed as kyn/trp ratio, is associated with response to immunotherapy; in particular, higher kyn/trp ratio could predict resistance to anti-PD-1 treatment VSports最新版本. These preliminary results suggest the possibility of using anti-PD-1 plus IDO inhibitor in those patients with high level of kyn/trp ratio. .

Keywords: Anti-PD-1; IDO; Immunotherapy; Kynurenine; Nivolumab V体育平台登录. .

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Figures (VSports app下载)

Fig. 1
Fig. 1
Correlation of serum kyn/trp ratio and serum quinolic acid concentration with immunotherapy response. Patients who showed an early progression (YES, n = 14) present a significantly higher concentration of kyn/trp ratio (a) and quinolic acid concentration (b) compared to patients who do not have an early progression (NO, n = 12). #p < 0.05 (Mann–Whitney test)
Fig. 2
Fig. 2
Correlation of serum kyn/trp ratio and quinolonic acid concentration with survival. Progression free survival (PFS, a) and overall survival (OS, b) were addressed by the Kaplan–Meier method and log-rank test
See this image and copyright information in PMC

References

    1. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974–1982. doi: 10.1200/JCO.2014.59.4358. - DOI - PMC - PubMed
    1. Horn L, Spigel DR, Vokes EE, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057) J Clin Oncol. 2017;35:3924–3933. doi: 10.1200/JCO.2017.74.3062. - DOI - PMC - PubMed
    1. Salati M, Baldessari C, Cerbelli B, Botticelli A. Nivolumab in pretreated non-small cell lung cancer: continuing the immunolution. Transl Lung Cancer Res. 2018 - PMC - PubMed
    1. Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive disease (HPD) is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23(8):1920–1928. doi: 10.1158/1078-0432.CCR-16-1741. - DOI - PubMed
    1. Badawy AA. Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int J Tryptophan Res. 2017;15(10):1178646917691938. - "V体育ios版" PMC - PubMed

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