Neutrophil Defensin Expression Correlated With Immune Checkpoint Response In Lung Cancer

Pixabay License | Source: mcmurryjulie , Altered aspect ratio.
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Lung cancer is the leading cause of cancer related death. Non-small cell lung cancer (NSCLC), comprises 80–85% of all lung cancer cases. Programmed cell death ligand 1 (PDL1) is an approved immunotherapeutic target in lung cancer patients. PDL1 expression by the tumour above a set threshold must be confirmed by companion immunohistochemistry (IHC) test in order for the patient to be eligible for PDL1 checkpoint inhibitor immunotherapy.

Unfortunately, not all eligible patients respond to checkpoint inhibitor therapy. A new study led by Geert Baggerman of University of Antwerp, Belgium, aimed to establish additional predictive biomarkers using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for successful immunotherapy, thus avoiding unnecessary costs and toxicities in patients who will not respond clinically. The results were published in the journal Cancers.

Neutrophil defensin 1, 2, and 3 were identified in tumour, but not normal lung tissue. They are antimicrobial peptides (AMPs) also known as ‘host defense peptides’. They are produced and released from the granules of neutrophils as a first line of defense against microbes. The defensin peptides were present in 7 out of 9 pretreatment biopsies of NSCLC patients with a positive response to anti-PD-L1 immunotherapy treatment, while they were present in only 2 out of 16 nonresponding patients. This was confirmed by IHC.

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Neutrophil defensins appeared capable of directing peripheral blood mononuclear cells (PBMCs) to attack the tumour cells. With further validation neutrophil defensins 1, 2, and 3 could be used to better stratify patients likely to respond to immune checkpoint inhibitors.

The study is limited by a small sample size and the mechanism of improved response to immunotherapy in the presence of neutrophil defensins 1, 2, and 3 was not confirmed.

“In this study, we used MALDI mass spectrometry imaging to study the distribution of immune-related peptides in relation to the anti-PD-(L)1 immunotherapy response. Since no prior knowledge of molecular identities is required for MALDI MSI experiments, crucial insights regarding immune-related peptide profiles can be obtained directly from tissues. Our differential expression analyses revealed three interesting peptides, namely, neutrophil defensin 1, 2 and 3,” concluded the authors