Prognostic Role of Soluble and Extracellular Vesicle-Associated PD-L1, B7-H3 and B7-H4 in Non-Small Cell Lung Cancer
Carlo Genova1,2, Roberta Tasso3,4, Alessandra Rosa5
1UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.
Abstract:
The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings. We evaluated the prognostic role of PD-L1 and of two B7 family members (B7-H3, B7-H4), both soluble and EV-associated, in a cohort of advanced NSCLC patients treated with first- (n = 56) or second-line (n = 126) ICIs. In treatment-naïve patients, high baseline concentrations of sPD-L1 (>24.2 pg/mL) were linked to worse survival, whereas high levels of sB7-H3 (>0.5 ng/mL) and sB7-H4 (>63.9 pg/mL) were associated with better outcomes. EV characterization confirmed the presence of EVs positive for PD-L1 and B7-H3, while only a small portion of EVs expressed B7-H4. The comparison between biomarker levels at the baseline and in the first radiological assessment under ICI-based treatment showed a significant decrease in EV-PD-L1 and an increase in EV-B7H3 in patients in the disease response to ICIs. Our study shows that sPD-L1, sB7-H3 and sB7-H4 levels are emerging prognostic markers in patients with advanced NSCLC treated with ICIs and suggests potential EV involvement in the disease response to ICIs.
Insights
Soluble PD-L1, B7-H3, and B7-H4 show promise as prognostic markers for non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). Extracellular vesicles may play a role in treatment response.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment, but efficacy is limited to a subset of patients.
- Soluble (s) and extracellular vesicle (EV)-associated immune checkpoints are potential biomarkers for ICI therapy.
Purpose of the Study:
- To evaluate the prognostic significance of soluble PD-L1, B7-H3, and B7-H4, and their EV-associated forms in advanced NSCLC patients treated with ICIs.
- To explore the dynamic changes of these biomarkers during ICI treatment in relation to treatment response.
Main Methods:
- Measured baseline levels of soluble PD-L1, B7-H3, and B7-H4 in 182 advanced NSCLC patients receiving first- or second-line ICIs.
- Characterized PD-L1, B7-H3, and B7-H4 expression on extracellular vesicles (EVs).
- Assessed changes in EV-PD-L1 and EV-B7-H3 levels from baseline to the first radiological assessment in relation to treatment response.
Main Results:
- High baseline sPD-L1 correlated with worse survival, while high sB7-H3 and sB7-H4 were associated with better outcomes in treatment-naïve patients.
- EVs were found to carry PD-L1 and B7-H3, with limited B7-H4 expression.
- Patients responding to ICIs showed a decrease in EV-PD-L1 and an increase in EV-B7-H3 levels during treatment.
Conclusions:
- Soluble PD-L1, B7-H3, and B7-H4 are emerging prognostic biomarkers for advanced NSCLC patients undergoing ICI therapy.
- Extracellular vesicles may be involved in the response to ICI treatment, suggesting their potential as dynamic predictive markers.
