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Gr-MDSC-linked asset as a potential immune biomarker in pretreated NSCLC receiving nivolumab as second-line therapy

Authors
  • Passaro, A.1
  • Mancuso, P.2
  • Gandini, S.2
  • Spitaleri, G.1
  • Labanca, V.2
  • Guerini-Rocco, E.2, 3
  • Barberis, M.2
  • Catania, C.1
  • Del Signore, E.1
  • de Marinis, F.1
  • Bertolini, F.2
  • 1 IEO, European Institute of Oncology IRCCS, Via G. Ripamonti, 435, Milan, 20141, Italy , Milan (Italy)
  • 2 IEO, European Institute of Oncology IRCCS, Milan, Italy , Milan (Italy)
  • 3 University of Milan, Milan, Italy , Milan (Italy)
Type
Published Article
Journal
Clinical & Translational Oncology
Publisher
Springer-Verlag
Publication Date
Jun 28, 2019
Volume
22
Issue
4
Pages
603–611
Identifiers
DOI: 10.1007/s12094-019-02166-z
Source
Springer Nature
Keywords
License
Yellow

Abstract

PurposeImmunotherapy is a new standard first-line treatment for non-small cell lung cancers (NSCLC) with high programmed cell death-ligand 1 (PD-L1) expression (≥ 50%) and second-line treatment regardless of PD-L1 status, though not all patients benefit from this approach. Much effort is ongoing to identify robust prognostic and predictive biomarkers of response to immune checkpoint inhibitors, overcoming PD-L1 that appears limited in its ability to discriminate patient candidates to this new class of anticancer agents. The purpose of this research study is to identify potential new biomarkers for immunotherapy in lung cancer.MethodsFifty-three consecutive patients with advanced NSCLC treated with nivolumab were enrolled in the study. All the patients received a blood analysis looking for the relationship between different populations of baseline white blood cells and granulocytic myeloid-derived suppressor cells (Gr-MDSC) detected by flow cytometry, to identify and characterize patients with poor likelihood of benefit from nivolumab in NSCLC second-line setting, regardless of clinical feature and PDL1 expression.ResultsUnivariate analysis showed that high baseline levels of Gr-MDSC and low baseline CD8/Gr-MDSC ratio are associated with significantly better (P = 0.02) response to immunotherapy treatment. Log-rank tests suggested a significant improvement in OS and PFS with high baseline levels of Gr-MDSC levels (≥ 6 cell/μl), low absolute neutrophil count (< 5840/μl), high eosinophil count (> 90 /μl), and NLR < 3. The multivariate analysis showed a statistically significant improvement for PFS (P = 0.003) and OS (P = 0.05) in favour of the identified good prognostic Gr-MDSC-linked asset group, compared with the poor prognosis group.ConclusionThe role of Gr-MDSC appears interesting as a potential biomarker in NSCLC patients receiving immune-checkpoint inhibitors. Further analyses are needed to confirmed and study in deep the role of these particular cells and their role in cancer response and progression during ICI therapy.

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