Original ResearchPredictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy
Introduction
Lung cancer is the leading cause of cancer death worldwide [1]. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancer cases, and approximately 30% of NSCLC patients present with stage III disease [2]. Concurrent chemoradiotherapy (CCRT) is the standard of care for these patients [3]. Despite intensive research into the treatment of NSCLC, the prognosis of patients with stage III disease remains poor, with a median survival time of approximately 20 months [4], [5], [6].
Programmed death 1 (PD1), which belongs to the CD28 family of proteins, is a receptor expressed on the surface of T cells that regulates their activation and proliferation. Its ligand, programmed death-ligand 1 (PD-L1), is frequently overexpressed in many types of human cancer [7]. The binding of PD-L1 to PD1 induces apoptosis or exhaustion in activated T cells, and blockade of this interaction has been shown to enhance the antitumour activity of T cells [7]. Antibody blockade of PD-1 with its ligand (PD-L1 and PD-L2) has shown promising efficacy against various malignancies, including NSCLC [8], [9], [10]. Preliminary observations of patients with recurrent cancers indicate that clinical responses to immune checkpoint blockers are associated with elevated tumour levels of immune inhibitory signals, such as PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and with increased numbers of tumour-infiltrating lymphocyte (TIL) [7], [11], [12], [13], [14], [15]. However, data on the prevalence and prognostic value of PD-L1 expression in NSCLC are limited, and the results of several studies involving small series have been inconsistent [16], [17], [18], [19], [20], [21], [22]. In addition, the clinical relevance of PD-L1 expression in stage III NSCLC patients who have received CCRT has remained unclear. In the present study, therefore, we examined PD-L1 expression and CD8+ TIL density in such patients and investigated their associated clinicopathologic characteristics, prognosis and predictive relevance.
Section snippets
Patients
We retrospectively screened consecutive patients who had been diagnosed as having stage III NSCLC at Kurume University Hospital and Yame General Hospital between 1999 and 2013. Patients who had been diagnosed pathologically as having NSCLC, who had received CCRT with combined platinum-containing chemotherapy, and for whom adequate histological specimens containing abundant tumour cells had been available were eligible for inclusion. The present study was conducted in accordance with the
Patient characteristics
The clinical characteristics of the 74 patients are shown in Table 1. The median age of the patients at diagnosis was 67 years (range, 43–81 years). Sixty-four (86%) of the patients were male, and 53 (72%) patients had a good performance status (PS) (0–1). The most predominant histological type was squamous cell carcinoma (40 patients), followed by adenocarcinoma (34 patients). Forty patients (54%) had stage IIIA disease and 34 (46%) had stage IIIB disease at the time of diagnosis. All patients
Discussion
Although blockade of the PD-1/PD-L1 pathway with monoclonal antibodies has recently emerged as a new therapeutic modality for NSCLC, the association between PD-L1 expression and prognosis in patients with stage III NSCLC has remained largely unknown. In the present study, we examined PD-L1 expression using IHC in stage III NSCLC patients who had received CCRT, and found that patients who showed positive expression of PD-L1 tended to show a poorer survival outcome than patients who were negative
Conflict of interest statement
The authors have no conflicts of interest to declare.
Acknowledgement
There was no funding source to acknowledge for this study.
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