PD-L1 expression in advanced NSCLC: Insights into risk stratification and treatment selection from a systematic literature review

Abstract

Tumors can evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Antibodies that block this pathway offer a promising new approach to treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic review of the literature was conducted to assess the association of PD-L1 with important patient and disease characteristics, the prognostic significance of PD-L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC. A total of 35 eligible studies were selected for analysis. Methods used to determine PD-L1 in NSCLC tissue varied considerably; with different PD-L1 antibodies, antibody detection methods, and staining cut-offs. Immunohistochemistry was the most frequent type of PD-L1 assay. Overall, study evidence did not support an association between PD-L1 expression and gender, age, smoking history, tumor histology (adenocarcinoma vs. squamous cell carcinoma), performance status, pathologic tumor grade or EGFR/KRAS/ALK mutational status. In several studies, high PD-L1 expression was associated with shorter survival compared with low expression. Most evidence indicated that patients with high vs. low PD-L1 expression were more likely to experience treatment benefit with anti-PD-1/PD-L1 agents (nivolumab, pembrolizumab, durvalumab, atezolizumab, and avelumab) in advanced NSCLC. Variability in the methods used to determine PD-L1 expression in NSCLC tissue suggests a need for standardized use of well-validated PD-L1 diagnostic assays. Although considerable research links PD-L1 expression in tumors to shorter survival in advanced/metastatic NSCLC, its use as a prognostic factor requires more study. As studies of anti-PD-1/PD-L1 agents continue, PD-L1 is likely to play an important role as a predictive biomarker for selecting patients deriving most benefit from anti-PD-1/PD-L1 monotherapy and directing patients with lower levels of tumor PD-L1 expression (with a high unmet medical need), to alternative treatments, such as combination immunotherapies.

Role of tumor-infiltrating lymphocytes in patients with solid tumors: Can a drop dig a stone?

“…Clinical trials of anti-PD-L1-directed therapy showed that PD-L1 overexpression in cell membranes of NSCLC patients could represent a valid biomarker of response and prognosis . Also, the response to immunotherapy [63,64] in advanced NSCLC patients can be predicted through the study of the tumor microenvironment . Also, a tumoral context dense of CD8+ [65] and FOXP3+ Treg TILs can be considered as predictive marker of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients , as well as high levels of the transforming [66,67] growth factor (TGF-) in TILs are predictive of poor post-operative β β survival .…”

Is there any correlation between spectral CT imaging parameters and PD‐L1 expression of lung adenocarcinoma?

“…The recent development of immunotherapy which targets the programmed death‐1/programmed death‐ligand 1 (PD‐L1) axis has been approved for first‐line treatment as well as second‐line treatments of NSCLC in many countries. It alone has significantly improved overall survival (OS) compared with chemotherapy for first‐line NSCLC with PD‐L1 TPS ≥50%, 20%, ≥1% . The higher the PD‐L1 expression, the better the objective response rate and median survival time.…”

“…Tumor proportion score (TPS) was counted. TPS >1% was positive and TPS >50% indicated a high expression of PD‐L1 …”

“…In addition to conventional chemotherapy, targeted therapies targeting epidermal growth factor receptor (EGFR) and receptor tyrosine kinase (ALK), which block mutant targets of lung adenocarcinoma, have become the first‐line treatment of choice . At the same time, programmed death ligand‐1 (PD‐L1) plays an important role in tumorigenesis and development, and promotes the wide application of immunotherapy in lung cancer …”

Evolution of immune escape mechanisms in the progression from preinvasive to invasive human lung adenocarcinoma

“…Heterogenous expression of PD-L1 among the solid tumor group 302 Expression of the PD-L1 checkpoint is a mechanism for immune escape in NSCLC and the 303 percent of cancer cells expressing PD-L1 is used clinically to assess overall PD-L1 expression 304 in tumors (19). In the p-NS tumor group only 3 of 25 tumors had greater than 1% PD-L1 + panCK…”