Circulating Tumor Cell PD-L1 Expression as Biomarker for Therapeutic Efficacy of Immune Checkpoint Inhibition in NSCLC

Abstract

Over the last decade, the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced non-small cell lung cancer (NSCLC) patients. PD-L1 tumor expression, along with tumor mutational burden, is currently being explored as a predictive biomarker for responses to immune checkpoint inhibitors (ICIs). However, lung cancer patients may have insufficient tumor tissue samples and the high bleeding risk often prevents additional biopsies and, as a consequence, immunohistological evaluation of PD-L1 expression. In addition, PD-L1 shows a dynamic expression profile and can be influenced by intratumoral heterogeneity as well as the immune cell infiltrate in the tumor and its microenvironment, influencing the response rate to PD-1/PD-L1 axis ICIs. Therefore, to identify subgroups of patients with advanced NSCLC that will most likely benefit from ICI therapies, molecular characterization of PD-L1 expression in circulating tumor cells (CTCs) might be supportive. In this review, we highlight the use of CTCs as a complementary diagnostic tool for PD-L1 expression analysis in advanced NSCLC patients. In addition, we examine technical issues of PD-L1 measurement in tissue as well as in CTCs.

CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma

“…Nevertheless, most of patients fail to respond to PD-1/PD-L1 axis inhibitors. The abnormal expression of PD-L1 can be used as a predictive or prognostic marker of PD-1/PD-L1 inhibition therapy for patients (31)(32)(33). However, few studies have studied the expression and regulatory mechanisms of PD-1 or PD-L1 expression in T-LBL (34,35).…”

Emerging Role of Circulating Tumor Cells in Gastric Cancer

“…Nonetheless, the predictive value of PD-L1 IHC is still controversial, since in various types of cancer, including GC, some patients with PD-L1 negative tumors also respond to anti-PD-1 therapy [96,97]. Recently, Cheng et al [65] found that in GC patients with negative PD-L1 in tumor tissue, the CTC Imaging flow cytometry signal was as varied as that of IHC staining, suggesting that expression of CTC PD-L1 is useful in the immunophenotypic differential diagnosis of tumors and thus can be a potential candidate for anti-PD-1/PD-L1 immune checkpoint therapy [98]. CTC level after checkpoint blockade therapy may be effective to predict poor prognosis in advanced GC [99].…”

Possibilities of Improving the Clinical Value of Immune Checkpoint Inhibitor Therapies in Cancer Care by Optimizing Patient Selection

“…Other potential soluble biomarkers include TCR diversity and clonality [89,90], as well as circulating immune cell subsets such as the number MDSCs or different T cell phenotypes [91][92][93]. The is evolving data on the negative prognostic meaning of PD-L1+ circulating tumor cells (CTCs) in NSCLC [94,95], however, the clinical benefit of immune checkpoint blockade in NSCLC based on PD-L1 status of circulating tumor cells remains uncertain. The prognostic role of soluble forms of PD-1 and PD-L1 (sPD-1, sPD-L1) on peripheral blood is unclear.…”