Evaluation of PD-L1 Expression and Systemic Inflammatory Blood Cell Ratios as Prognosticators in Advanced Lung,...

Immunotherapy with immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis has become an established treatment strategy across various malignancies. In this context, PD-L1 expression plays a key role in the clinical management of cancer patients. However, the prognostic significance of PD-L1 expression remains inconsistent across different cancer types. This study aimed to evaluate the prevalence of PD-L1 expression in three cancer types and to examine its association with key clinicopathological parameters, systemic inflammatory markers and patient outcomes.

A retrospective cohort of 141 patients with lung, breast and head and neck cancers diagnosed between 2016 and 2021 was analysed. PD-L1 expression was analysed by immunohistochemistry using clone 22C3 and the scoring system for positivity was determined according to standard clinical scoring practices for each tumour type. Systemic inflammatory markers, including the platelet-to-lymphocyte ratio (PLR), were calculated from pre-treatment blood counts. Correlation and survival analyses were performed to evaluate the associations between PD-L1 expression levels, clinicopathological characteristics and prognosis. Bioinformatics analyses using GeneMania, STRING and TIMER (v.3) databases were conducted to explore functional enrichment, protein-protein interactions and immune-cell infiltration associated with PD-L1 expression.

PD-L1 positivity (≥1%) was observed in 56.75% of lung cancer cases, 44% of breast cancer cases and 92.85% of head and neck cancer cases. PD-L1 expression alone was not significantly associated with overall survival across the cancer cohorts. However, it was significantly associated with PLR in the lung cancer cohort (p = 0.036). Notably, low PLR was associated with improved survival in both lung cancer (p = 0.007) and breast cancer (p = 0.031). Bioinformatics analysis identified several PD-L1-interacting genes, including PD-1, CTLA4 and PTPN and demonstrated strong positive correlations between PD-L1 expression and the infiltration of CD8+ T cells, neutrophils and dendritic cells across the analysed malignancies.

Despite its high expression in advanced solid tumours, PD-L1 showed limited prognostic value in our cancer cohort. In contrast, systemic inflammatory markers particularly PLR, emerged as a potential indicator of clinical outcome. Our data suggest that integrating PD-L1 status with systemic inflammatory markers may improve outcome prediction and help inform therapeutic decision-making in patients with advanced malignancies.