Survival analysis with regard to PD‑L1 and CD155 expression in human small cell lung cancer and a comparison with associated receptors

Abstract

Immune checkpoints expressed on tumor cells may suppress the cytotoxicity of tumor-infiltrating lymphocytes (TILs) via interaction with their ligands. In the present study, checkpoint proteins and ligands, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cluster of differentiation (CD)155 and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) were systematically analyzed in patients with small cell lung cancer (SCLC). Furthermore their clinicopathological features and survival rates were investigated. Immunohistochemistry was performed in order to analyze the expression of PD-L1, CD155, PD-1 and TIGIT in 60 patients with SCLC, and survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. It was reported that CD155/TIGIT and PD-L1/PD-1 were highly expressed on tissues of surgically resected SCLC. High expression levels of PD-L1, CD155 or PD-L1+CD155 were significantly associated with shorter survival. However, high expression levels of PD-1 or TIGIT exhibited no obvious association with shorter survival time. Moreover, patients with SCLC in whom PD-L1 and CD155 levels were highly expressed had the shortest survival rate. Multivariate survival analysis revealed that highly expressed PD-L1 [hazard ratio (HR)=2.55, 95% confidence interval (CI)=1.18–5.51, P=0.017] and CD155 (HR=2.40, 95% CI=1.05–5.50, P=0.038) were independent prognostic factors for overall survival (OS) time in SCLC. In addition, it was reported that TIGIT and PD-1, the receptors of CD155 and PD-L1, respectively, were also constitutively expressed on CD8 + TILs and tumor cells in SCLC. High expression levels of PD-L1 and CD155 were independent prognostic factors for OS time in patients with SCLC.

Repositioning liothyronine for cancer immunotherapy by blocking the interaction of immune checkpoint TIGIT/PVR

“…As shown in Fig. 1a, PVR expressed in head and neck cancer (HNSC), lung adenocarcinoma (LUAD) and stomach cancer (STAD), which was consistent with the previous study [13,15,33]. In addition, it also expressed across a broad spectrum of cancers including bladder cancer (BLCA), endometrioid cancer (UCEC), esophageal cancer (ESCA), kidney chromophobe (KICH), Kidney papillary cell carcinoma (KIRP), prostate cancer (PRAD), thyroid cancer (THCA), and especially in colon cancer (COAD) and rectal cancer (READ) within 50 datasets.…”

Prognostic and Clinicopathological Value of Programmed Cell Death Ligand1 Expression in Patients With Small Cell Lung Cancer: A Meta-Analysis

“…A total of 20 full-text articles were excluded for the following reasons: 12 lacked necessary information, three were editorials, two were letters, two did not report using an IHC method, and one was a review. Finally, nine articles (8)(9)(10)(11)(12)(13)(14)(15)(16) published between 2015 and 2019 were included in this meta-analysis. The selection flowchart is displayed in Figure 1.…”

“…The baseline characteristics of the included studies are shown in Table 1. Five studies were performed in China (11,(13)(14)(15)(16), two in Japan (8,9), and one each in Taiwan (10), and Italy (12), respectively. The total sample size was 921, ranging from 40 to 205.…”

“…A recent randomized, controlled, phase 3 trial showed that the combination of the PD-L1 inhibitor atezolizumab and chemotherapy as the first-line treatment results in significantly longer survival than that following chemotherapy alone in patients with extensive-stage SCLC (7). Previous studies have also investigated the prognostic role of PD-L1 in patients with SCLC, which revealed inconsistent results (8)(9)(10)(11)(12)(13)(14)(15)(16). For example, some reports suggested that high PD-L1 expression is correlated with poor overall survival (OS) in patients with SCLC (10,15).…”

“…Previous studies have also investigated the prognostic role of PD-L1 in patients with SCLC, which revealed inconsistent results (8)(9)(10)(11)(12)(13)(14)(15)(16). For example, some reports suggested that high PD-L1 expression is correlated with poor overall survival (OS) in patients with SCLC (10,15). On the contrary, other studies demonstrated that PD-L1 overexpression is an independent prognostic factor of favorable OS in patients with SCLC (8,13,14).…”