PD-L1 heterogeneity in patients with non-small cell lung cancer

Aims Programmed death receptor ligand-1 (PD-L1) expression has been identified as the main predictor of responsiveness to programmed death receptor-1 (PD-1)-targeted immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). In this retrospective study, we explored the inter- and intratumoral PD-L1 heterogeneity in patients who received two separate pathologically verified NSCLC diagnoses at Shandong Provincial Hospital Affiliated to Shandong First Medical University and Linyi People's Hospital. Methods Patients were classified into four groups according to the type of intra- and intertumoral heterogeneity: Group 1 included patients in whom primary tumor heterogeneity was observed between biopsy and surgical specimens; in Group 2, heterogeneity was observed between primary tumors and paired dissected regional lymph nodes; in Group 3, heterogeneity was observed between resected primary tumors and distant metastases or recurrent disease; in Group 4, heterogeneity was observed before and after microwave ablation. Of the 221 enrolled patients, 97, 36, 57, and 31 were allocated to groups 1, 2, 3, and 4, respectively. Results Significant heterogeneity was observed among all patients (P = 0.026) and within Group 1 (P = 0.022) when using a PD-L1 tumor proportion score (TPS) cut-off of 5%. However, no heterogeneity was observed in the other groups or with a PD-L1 TPS cut-off value of 1%. Conclusions Intratumoral PD-L1 expression heterogeneity between the biopsy and surgical specimens of primary tumors was more frequently detected than intertumoral heterogeneity in advanced NSCLC.