Prognostic impact of PD-L1 and TIGIT expression in non-small cell lung cancer following concurrent chemo-radiotherapy

Abstract

We investigated the effect of preoperative therapy for non-small cell lung cancer on programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), poliovirus receptor (CD155), and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) expression and prognosis with the cases of 28 patients received preoperative concurrent chemo-radiotherapy (cCRT) and 27 received preoperative drug therapy. The post-treatment PD-L1 expression was higher in cCRT group than in the drug therapy (50.0% vs 5.0%, p = 0.000), whereas that of CD155 did not significantly differ (40.0% vs 60.0%, p = 0.131). The PD-1 expression was not significantly different between the cCRT and drug therapy groups (51.1% vs 42.9%, p = 0.076), while the TIGIT was significantly higher in the cCRT group (41.5% vs 34.0%, p = 0.008). The patients who received cCRT resulted in elevated PD-L1and TIGIT values had a worse prognosis (p = 0.008). The PD-L1 and TIGIT expression after cCRT was significantly higher than after drug treatment. The cCRT population with high expression of both had a significantly poorer prognosis, indicating elevation of PD-L1 and TIGIT after cCRT as a negative prognostic factor. Combination therapy with anti-PD-L1 and anti-TIGIT antibodies after cCRT may contribute to an improved prognosis.

Real-world outcomes with durvalumab after chemoradiotherapy in patients with unresectable stage III NSCLC: interim analysis of overall survival from PACIFIC-R

“… 22 , 23 For example, PD-L1 expression can vary according to anatomical sites and the immunohistochemistry assays used to determine expression. 22 Moreover, RT can induce up-regulation of tumoral PD-L1 expression, 24 , 25 which is relevant in the context of the PACIFIC regimen as tumoral PD-L1 expression is typically determined from tumor samples obtained before receiving CRT. The label approved for durvalumab by the EMA excludes patients with PD-L1 expression on <1% of TCs based on a post hoc analysis, 7 , 12 while similar restrictions are not applied by other regulatory bodies, including the United States FDA.…”

Prognostic factors of resected pathological stage I lung adenocarcinoma: evaluating subtypes and PD-L1/CD155 expression

“…We previously reported that p-stage I adenocarcinoma expressing both CD155 and PD-L1 has a significantly poorer prognosis 15 . Moreover, NSCLC expressing both PD-L1 and TIGIT (ligand for CD155) has a poorer prognosis after neoadjuvant chemoradiotherapy 14 . Sun et al 23 reported that CD155 expression is an independent poor prognostic factor in 334 lung adenocarcinomas (including 137 p-stages II–IV).…”

“…Cancer cells suppress T-lymphocyte activity by expressing TIGIT ligands, such as CD155, also known as poliovirus receptor (PVR) 11 . Accordingly, blockade of the TIGIT/CD155 axis has also emerged as a novel therapeutic strategy for various malignant tumours, including lung cancer 12 – 14 .…”

Clinicopathological characteristics correlated with programmed cell death-ligand 1 expression in advanced lung adenocarcinoma

“…Some studies have shown that PD-L1 is a biomarker indicating a poor prognosis and a low survival rate in patients with advanced NSCLC ( 48 - 50 ). When discussing the influence of clinicopathological data on PD-L1 expression, we were surprised to find that T and M staging, especially the T stage, were significantly negatively correlated with PD-L1 levels.…”