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Open AccessArticle

Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients

1
Centre for Proteomics, University of Antwerp, 2020 Antwerpen, Belgium
2
Health Unit, VITO, 2400 Mol, Belgium
3
Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium
4
Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
5
Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium
6
Food & Bio-Based Products, AgResearch Ltd., Lincoln 7674, New Zealand
7
Thoracic Oncology Department, Antwerp University Hospital, 2650 Edegem, Belgium
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 863; https://doi.org/10.3390/cancers12040863
Received: 5 March 2020 / Revised: 30 March 2020 / Accepted: 1 April 2020 / Published: 2 April 2020
(This article belongs to the Special Issue The Cancer Proteome)
(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies ([email protected]); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC. These results were verified and confirmed with immunohistochemical analyses. In addition, we provide in-vitro evidence of the immune stimulatory effect of neutrophil defensins towards cancer cells; and (4) Conclusions: With proteomic approaches, we have discovered neutrophil defensins as additional prospective biomarkers for an anti-PD-(L)1 immunotherapy response. Thereby, we also demonstrated that the neutrophil defensins contribute in the activation of the immune response towards cancer cells, which could provide a new lead towards an anticancer therapy. View Full-Text
Keywords: mass spectrometry imaging; immunotherapy; non-small cell lung cancer; predictive protein biomarkers; neutrophil defensins mass spectrometry imaging; immunotherapy; non-small cell lung cancer; predictive protein biomarkers; neutrophil defensins
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MDPI and ACS Style

Berghmans, E.; Jacobs, J.; Deben, C.; Hermans, C.; Broeckx, G.; Smits, E.; Maes, E.; Raskin, J.; Pauwels, P.; Baggerman, G. Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients. Cancers 2020, 12, 863.

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