Most patients (67.1%) had a tumor size larger than 3 cm. ( em P /em =0.023, em P /em =0.000, and em P /em =0.009, respectively), but only stage was found to be an independent factor for OS ( em P /em =0.007), and PD-L1 expression status showed a trend to be independently correlated with OS ( em P /em =0.080). Conclusion Our results showed that a large proportion of patients with pulmonary LELC had positive expression of PD-L1, supporting the potential use of anti-PD-1/PD-L1-targeted therapies in this distinct type of NSCLC. strong class=”kwd-title” Keywords: pulmonary lymphoepithelioma-like carcinoma, programmed cell death-ligand 1, Epstein-Barr virus, tumor-infiltrating lymphocytes, prognosis Introduction Primary pulmonary lymphoepithelioma-like carcinoma (LELC) was first reported by Begin et al1 in 1987, and is classified as a type of large-cell carcinoma based on the World Health Organization classification.2 Histopathologically, it is similar to nasopharyngeal carcinoma,3 and has a close relationship with Epstein-Barr virus (EBV) infection.4 Over the past two decades, fewer than 300 cases have been reported in the literature, including no more than 20 cases from Western populations.5,6 Patients with lung LELC have better outcomes than those with adenocarcinoma or squamous cell carcinoma of the lung.7 Radical surgery is usually performed in early-stage disease. For advanced disease, the treatment strategy is still controversial due to AZ191 the rarity of lung LELC, and a combination of chemotherapy, surgery, and radiotherapy could be considered. Epidermal growth factor receptor (EGFR) mutations8 and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene9 have been found to be driver genes in some patients with non-small cell lung cancer (NSCLC). Patients who harbor EGFR mutations are sensitive to EGFR tyrosine kinase inhibitors10 and those with EML4-ALK respond well to crizotinib.11 However, EGFR mutations and ALK rearrangement have been reported to be rare in pulmonary LELCs,6,12 suggesting that EGFR-targeted and ALK-targeted therapies are not suitable for patients with advanced pulmonary LELC. Thus, other treatment approaches, such as immune therapies, should be investigated to improve the outcome of patients with advanced pulmonary LELC. Tumor-infiltrating lymphocytes AZ191 (TILs) are generally considered to reflect the primary host immune response against tumors. However, in patients with various types of cancer, the immune system is often characterized by the presence of a variety of inhibitory mechanisms preventing lymphocyte activation.13 Programmed cell death receptor 1 (PD-1) is typically expressed by activated lymphocytes.14 Its engagement by specific ligands, including PD ligand 1 (PD-L1) and PD ligand 2, triggers downregulation of antigen-stimulated lymphocyte proliferation and cytokine production,15,16 ultimately resulting in lymphocyte exhaustion and induction of immune tolerance.17,18 Recently, a number of studies have found upregulated expression of PD-1 ligands in malignant cells, which has been suggested to play a central role in tumor-immune system interaction. Thus, by triggering PD-1, cancer cells might shut down specific immune responses.19 PD-L1 has been reported to be expressed by tumor cells of different origin, including renal cell carcinoma,20 squamous cell carcinoma of Rabbit Polyclonal to OR2T2 the head and neck,21 esophageal cancer,22 and NSCLC.23 Capitalizing on this background, PD-1/PD-L1 blockade by anti-PD-1 or anti-PD-L1 monoclonal antibodies has been envisaged as an appealing option to activate the host immune system to eradicate tumors. Recently, promising results of Phase I clinical trials involving patients bearing a variety of malignancies have been published.24C26 In particular, blocking of antibodies against PD-1 and PD-L1 has shown clinical activity in NSCLC. Due to the rarity of pulmonary LELC, little is known about the biology of this neoplasm. In this work, we investigated the expression status of PD-L1 in patients with AZ191 pulmonary LELC. Our results showed that a large proportion of patients with pulmonary LELC AZ191 had positive expression of PD-L1, supporting the potential use of anti-PD-1/PD-L1-targeted therapies in this distinct type of NSCLC. Materials and methods Patients A total of 79 consecutive patients with pulmonary LELC from January 2001 to December 2013 were enrolled in this study. As previously reported, 6 patients with negative EBV-encoded RNA staining were excluded from this study. Nasopharyngoscopy or positron emission tomography-computed tomography was conducted to rule out lung metastasis from nasopharyngeal carcinoma. Sun Yat-sen University Cancer Center research ethics board approved use of the data AZ191 in this study, and informed consent for use and publication of patients medical information was obtained from all patients at their first visit. We restaged all patients based on the American.