| Title |
Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?
|
|---|---|
| Published in |
Journal of Translational Medicine, August 2018
|
| DOI | 10.1186/s12967-018-1595-3 |
| Pubmed ID | |
| Authors |
Andrea Botticelli, Bruna Cerbelli, Luana Lionetto, Ilaria Zizzari, Massimiliano Salati, Annalinda Pisano, Mazzuca Federica, Maurizio Simmaco, Marianna Nuti, Paolo Marchetti |
| Abstract |
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. 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. 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. 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. 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 = 0.005, 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). 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. These preliminary results suggest the possibility of using anti-PD-1 plus IDO inhibitor in those patients with high level of kyn/trp ratio. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 67% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 93 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 15 | 16% |
| Student > Ph. D. Student | 14 | 15% |
| Researcher | 11 | 12% |
| Student > Bachelor | 7 | 8% |
| Other | 7 | 8% |
| Other | 11 | 12% |
| Unknown | 28 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 22 | 24% |
| Biochemistry, Genetics and Molecular Biology | 14 | 15% |
| Immunology and Microbiology | 8 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 8% |
| Agricultural and Biological Sciences | 5 | 5% |
| Other | 8 | 9% |
| Unknown | 29 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 July 2022.
All research outputs
#6,413,935
of 22,788,370 outputs
Outputs from Journal of Translational Medicine
#986
of 3,988 outputs
Outputs of similar age
#113,039
of 329,794 outputs
Outputs of similar age from Journal of Translational Medicine
#15
of 84 outputs
Altmetric has tracked 22,788,370 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 3,988 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. This one has gotten more attention than average, scoring higher than 74% of its peers.
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We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.