FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer.
Peter GrellSimona BorilovaPavel FabianIveta SelingerováDavid NovakPetr MullerIgor KissRostislav VyzulaPublished in: Cancers (2023)
Immune checkpoint inhibitors (ICI) are the main therapy currently used in advanced malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Despite the wide variety of uses, the possibility of predicting ICI efficacy in these tumor types is scarce. The aim of our study was to find new predictive biomarkers for ICI treatment. We analyzed, by immunohistochemistry, various cell subsets, including CD3+, CD8+, CD68+, CD20+, and FoxP3+ cells, and molecules such as LAG-3, IDO1, and TGFβ. Comprehensive genomic profiles were analyzed. We evaluated 46 patients with advanced MM (31) and NSCLC (15) treated with ICI monotherapy. When analyzing the malignant melanoma group, shorter median progression-free survival (PFS) was found in tumors positive for nuclear FoxP3 in tumor-infiltrating lymphocytes (TILs) ( p = 0.048, HR 3.04) and for CD68 expression ( p = 0.034, HR 3.2). Longer PFS was achieved in patients with tumors with PD-L1 TPS ≥ 1 ( p = 0.005, HR 0.26). In the NSCLC group, only FoxP3 positivity was associated with shorter PFS and OS. We found that FoxP3 negativity was linked with a better response to ICI in both histological groups.
Keyphrases
- regulatory t cells
- small cell lung cancer
- free survival
- poor prognosis
- dendritic cells
- advanced non small cell lung cancer
- peripheral blood
- induced apoptosis
- immune response
- cell proliferation
- clinical trial
- stem cells
- combination therapy
- randomized controlled trial
- copy number
- signaling pathway
- oxidative stress
- climate change
- risk assessment
- gene expression
- long non coding rna
- open label
- bone marrow
- transforming growth factor
- mesenchymal stem cells
- tyrosine kinase
- double blind