Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients
(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 lun...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/4/863 |
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| author | Eline Berghmans Julie Jacobs Christophe Deben Christophe Hermans Glenn Broeckx Evelien Smits Evelyne Maes Jo Raskin Patrick Pauwels Geert Baggerman |
| author_facet | Eline Berghmans Julie Jacobs Christophe Deben Christophe Hermans Glenn Broeckx Evelien Smits Evelyne Maes Jo Raskin Patrick Pauwels Geert Baggerman |
| author_sort | Eline Berghmans |
| collection | DOAJ |
| description | (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. |
| first_indexed | 2024-03-10T20:43:02Z |
| format | Article |
| id | doaj.art-8355bdf9f3744cada088302bda9a4840 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:43:02Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8355bdf9f3744cada088302bda9a48402023-11-19T20:31:32ZengMDPI AGCancers2072-66942020-04-0112486310.3390/cancers12040863Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC PatientsEline Berghmans0Julie Jacobs1Christophe Deben2Christophe Hermans3Glenn Broeckx4Evelien Smits5Evelyne Maes6Jo Raskin7Patrick Pauwels8Geert Baggerman9Centre for Proteomics, University of Antwerp, 2020 Antwerpen, BelgiumCenter for Oncological Research, University of Antwerp, 2610 Wilrijk, BelgiumCenter for Oncological Research, University of Antwerp, 2610 Wilrijk, BelgiumCenter for Oncological Research, University of Antwerp, 2610 Wilrijk, BelgiumCenter for Oncological Research, University of Antwerp, 2610 Wilrijk, BelgiumCenter for Oncological Research, University of Antwerp, 2610 Wilrijk, BelgiumFood & Bio-Based Products, AgResearch Ltd., Lincoln 7674, New ZealandThoracic Oncology Department, Antwerp University Hospital, 2650 Edegem, BelgiumCenter for Oncological Research, University of Antwerp, 2610 Wilrijk, BelgiumCentre for Proteomics, University of Antwerp, 2020 Antwerpen, Belgium(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.https://www.mdpi.com/2072-6694/12/4/863mass spectrometry imagingimmunotherapynon-small cell lung cancerpredictive protein biomarkersneutrophil defensins |
| spellingShingle | Eline Berghmans Julie Jacobs Christophe Deben Christophe Hermans Glenn Broeckx Evelien Smits Evelyne Maes Jo Raskin Patrick Pauwels Geert Baggerman Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients Cancers mass spectrometry imaging immunotherapy non-small cell lung cancer predictive protein biomarkers neutrophil defensins |
| title | Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients |
| title_full | Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients |
| title_fullStr | Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients |
| title_full_unstemmed | Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients |
| title_short | Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients |
| title_sort | mass spectrometry imaging reveals neutrophil defensins as additional biomarkers for anti pd l 1 immunotherapy response in nsclc patients |
| topic | mass spectrometry imaging immunotherapy non-small cell lung cancer predictive protein biomarkers neutrophil defensins |
| url | https://www.mdpi.com/2072-6694/12/4/863 |
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