FBP 90440 Cancers 12(4)_863 - EBerghmans et al 020420.pdf (5.86 MB)

Mass spectrometry imaging reveals neutrophil defensins as additional biomarkers for anti-PD-(L)1 immunotherapy response in NSCLC patients

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posted on 2023-05-03, 20:09 authored by Eline Berghmans, Julie Jacobs, Christophe Deben, Christophe Hermans, Glenn Broeckx, Evelien Smits, Evelyne MaesEvelyne Maes, Jo Raskin, Patrick Pauwels, Geert Baggerman
(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 (Biobank@UZA); (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.


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Berghmans, E., Jacobs, J., Deben, C., Hermans, C., Broeckx, G., Smits, E., … Baggerman, G. (2020). Mass spectrometry imaging reveals neutrophil defensins as additional biomarkers for anti-PD-(L)1 immunotherapy response in NSCLC patients. Cancers, 12(4), 863. doi:10.3390/cancers12040863

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