Inflammatory and autoimmune predictive markers of response to anti-PD-1/PD-L1 therapy in NSCLC and melanoma
Aram A Musaelyan1,2, Sergey V Lapin1, Margarita A Urtenova3
1Laboratory for Diagnostics of Autoimmune Diseases, Center for Molecular Medicine, Pavlov First Saint Petersburg State Medical University, Saint Petersburg 197022, Russia.
Abstract:
Immune checkpoint inhibitors (ICI) are a standard in cancer therapy, but few patients respond to the treatment. The aim of the present study was the determination of immunological markers for monitoring response to ICI. The present study included 74 patients receiving ICI in subsequent [group 1; non-small cell lung cancer (NSCLC)] and first-line setting (group 2; melanoma) and 30 patients with NSCLC receiving first-line chemotherapy. In groups 1 and 2 β-2 microglobulin (B2-MG), neopterin (NPT), IL-6, IL-18, HLA-DRB1 and autoantibodies were assessed after two months of ICI, and before the start of next administration in group 3. In group 1 low level of B2-MG (P<0.0001), NPT (P<0.0001), IL-6 (P<0.0001), IL-18 (P=0.0003), HLA-DRB1*03 (P=0.016) and anti-TPO antibodies (P=0.016) were associated with response >six months. In group 2 high level of B2-MG (P=0.0001), NPT (P=0.0016), IL-6 (P=0.013) and IL-18 (P=0.032) were associated with early disease progression (
Insights
Immune checkpoint inhibitors (ICI) show promise in cancer treatment. This study identified immunological markers like B2-MG and NPT that can help predict patient response to ICI therapy.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICI) are a cornerstone of modern cancer therapy.
- However, a significant proportion of patients do not respond to ICI treatment, necessitating the identification of predictive biomarkers.
- Monitoring treatment response is crucial for optimizing patient outcomes.
Purpose of the Study:
- To determine immunological markers for monitoring response to immune checkpoint inhibitors (ICI).
- To investigate the association of specific biomarkers with treatment response and progression-free survival (PFS) in non-small cell lung cancer (NSCLC) and melanoma patients receiving ICI.
- To compare biomarker levels in ICI-treated patients with those receiving chemotherapy.
Main Methods:
- The study included 74 patients receiving ICI (NSCLC and melanoma) and 30 NSCLC patients receiving chemotherapy.
- Assessed biomarkers included β-2 microglobulin (B2-MG), neopterin (NPT), IL-6, IL-18, HLA-DRB1, and autoantibodies.
- Statistical analyses, including univariate and multivariate analyses, were employed to identify predictive markers for response and PFS.
Main Results:
- In NSCLC patients receiving ICI, low levels of B2-MG, NPT, IL-6, IL-18, HLA-DRB1*03, and anti-TPO antibodies were associated with response >6 months.
- In melanoma patients receiving ICI, high levels of B2-MG, NPT, IL-6, and IL-18 correlated with early disease progression (<6 months).
- Immune-related adverse events predicted prolonged PFS; high neutrophil-lymphocyte ratio and elevated B2-MG/NPT levels predicted shorter PFS in specific groups.
Conclusions:
- Immunological markers such as B2-MG and NPT show potential as predictive biomarkers for ICI therapy response.
- Specific biomarker profiles may differentiate between responders and non-responders, and predict disease progression.
- Further prospective studies are warranted to validate these findings and their clinical utility in immunotherapy.
