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41 CD39 affect the prognostic role of NLR via N2 neutrophils in metastatic melanoma patients treated with immunotherapy
  1. Domenico Mallardo1,
  2. Mario Fordellone2,
  3. Andrew White3,
  4. Margaret Ottaviano1,
  5. Francesca Sparano1,
  6. Michael Bailey4,
  7. Bianca Arianna Facchini1,
  8. SuFey Ong3,
  9. Piera Maiolino1,
  10. Corrado Caraco1,
  11. Sarah Church3,
  12. Ernesta Cavalcanti1,
  13. Sarah Warren5,
  14. Alfredo Budillon6,
  15. Alessandra Cesano7,
  16. Ester Simeone1,
  17. Paolo Chiodini2 and
  18. Paolo Ascierto1
  1. 1Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
  2. 2Universitiy of Campania ‘Luigi Vanvitelli’, 81100 Naples, Italy., Naples, Italy
  3. 3NanoString Technologies, Seattle, WA, USA
  4. 4NanoString Technologies, Tukwila, WA, USA
  5. 5Kite, A Gilead Company, Seattle, WA, USA
  6. 6National Cancer Institute G. Pascale, Napoli, Italy
  7. 7ESSA Pharma Inc., South San Francisco, CA, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background The immune checkpoint inhibitors (ICIs) revolutionized cancer therapeutic landscape and substantially improved the survival of patients (pts) with advanced malignancies. Several predictive biomarkers are under evaluation, in order to identify patients who can benefit from ICI. Recently, elevated NLR, calculated from absolute neutrophil count and white cell count, were found to be independent predictors of reduced survival and increased risk of progression in melanoma patients receiving ICI. The purpose of this study is to retrospectively investigate relationship of NLR with inflammation-immune mediators.

Methods Gene profiling analysis was performed from 78 basal PBMCs of metastatic melanoma pts treated in first line with anti-PD1 using NanoString IO360 panel. Patient’s characteristics are listed in table 1. To identify the best genes signature the Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was applied.

Results Overall, 78 patients were included in the analysis. Pts with high NLR at baseline (ratio >5.57) had a poorer PFS (HR=7.27, 95% CI = 3.57–14.8; p < 0.0001) and OS (HR=3.98; 95% CI = 2.0–7.9) than the pts with low NLR. Brain metastases were present in a higher proportion of pts with high NLR compared to those with low NLR (p=0.01). In the trascriptomic analysis, NLR was associated with SH2D1A, CD3, ZAP70, CD45RA genes, while a high NLR with CCNA1, LDHA, IL18R1, CD39, PTEN, MYD88 and MMP9 genes (ROC curve, AUC=0.97, p<0001). The signatures are also associated to response. In addition, CD39 expression is higher in NLR high and is associate with increase of N2 neutrophils. NLR increase on treatment is also associated to worse outcome and a specific genetic signature.

Conclusions NLR high is related with immunosuppressive, inflammatory and tumor related genes; in particular with N2 neutrophils associate to adenosine pathway activation. This could explain the prognostic role of NLR. Further investigations are needed to get additional information.

Acknowledgements This work was supported by the Italian Ministry of Health Ricerca Corrente funds

Ethics Approval This study was approved by the Ethics Committee of Istituto Nazionale Tumori—IRCCS—Fondazione ‘G. Pascale’, Naples, Italy, protocol number 17/17 oss. All patients released informed consent to participate.

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Abstract 41 Table 1

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