AI Article Synopsis

  • Novel immunotherapies for lung cancer can reactivate the immune system for tumor cell killing, but many patients experience treatment failure, particularly women, possibly due to the immunosuppressive glycoprotein glycodelin.
  • Research shows that glycodelin from non-small-cell lung cancer (NSCLC) resembles that from amniotic fluid and interacts with immune cells, potentially affecting inflammatory responses and tumor dynamics.
  • High levels of glycodelin in tumors are linked to poor survival rates in female patients and may serve as a biomarker to identify those who won't benefit from immunotherapy, suggesting it could also be targeted for improved treatment options.

Article Abstract

Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. NSCLC-derived glycodelin interacts with immune cells in vitro and regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. In tumor microarray samples of patients, high glycodelin staining in tumor areas results in an impaired overall survival of female patients. Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trsl.2024.02.007DOI Listing

Publication Analysis

Top Keywords

lung cancer
16
female patients
12
glycodelin
9
nsclc-derived glycodelin
8
tumor
5
patients
5
pregnancy-associated protein
4
protein glycodelin
4
glycodelin potential
4
potential sex-specific
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!