Potential Role of Circulating PD-L1⁺ Leukocytes as a Predictor of Response to Anti-PD-(L)1 Therapy in NSCLC Patients

PD-(L)1 inhibitors are part of the treatment strategy for non-small cell lung cancer (NSCLC) although its efficacy is limited to certain patients. Our study aimed to identify patients who might benefit from anti-PD-(L)1 inhibitors by analyzing the PD-L1 expression on circulating leukocytes and its evolution during treatment. One hundred thirteen NSCLC patients, according to their radiological response after 10-12 weeks of treatment, were classified into responders, stable, and progressive disease. Percentages of circulating PD-L1⁺ leukocytes, PD-L1⁺ platelets (PLTs), and leukocyte-PLT complexes were assessed using flow cytometry, and plasma concentrations of soluble immunomodulatory factors were quantified by ELISA. Responders exhibited significantly higher pre-treatment percentages of PD-L1⁺ neutrophils, PD-L1⁺ CD14⁺ cells, and PD-L1⁺ PLTs than progressors. The percentages of these populations decreased in responders post-treatment, contrasting with stables and progressors. PLTs notably contributed to PD-L1 expression in CD14⁺ cells and neutrophils. Plasma cytokine analysis revealed baseline differences only in IL-17 concentration among groups, whereas network analyses highlighted distinct association patterns between plasma molecules and PD-L1⁺ leukocytes after 10-12 weeks of treatment. Our findings suggest that pre-treatment assessment of circulating PD-L1⁺ neutrophils, PD-L1⁺ CD14⁺ cells, and PD-L1⁺ PLTs may be helpful in identifying NSCLC patients who are potential candidates for anti-PD-(L)1 therapy.