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.

Background: B and T lymphocyte attenuator (BTLA) is a novel immune checkpoint with an unclear role in non-small-cell lung cancer (NSCLC). In contrast, the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint is a potentially curative immunotherapy target in NSCLC. Our study investigated BTLA expression and its relationship with PD-1/PD-L1, tumor-infiltrating lymphocytes (TILs), and clinicopathological features. Methods: The protein expressions of BTLA, PD-1, and PD-L1 were evaluated by immunohistochemistry (IHC) and TIL abundance was scored in paraffin-embedded tissues from surgically resected specimens from 87 patients with stage I-III NSCLC. Results: BTLA was expressed in tumor cells in 35 patients with NSCLC (40.2%). In addition, 42 patients (48.3%) were positive for PD-1 in TILs and 31 (35.6%) were positive for PD-L1 in tumor cells. BTLA was overexpressed in patients with lymphatic invasion (P=0.045) and an advanced tumor stage (P=0.034). High expression of BTLA was positively correlated with a high level of PD-L1 (P=0.011). Patients with positive BTLA expression had a shorter relapse-free survival (RFS) than those with negative BTLA expression (P=0.029). Moreover, patients negative for both BTLA and PD-L1 had a longer RFS than patients who were positive for BTLA or PD-L1 or for both checkpoints (P=0.012). The same pattern was shown for overall survival (P=0.031). Conclusion: High BTLA expression may predict poor prognosis in patients with NSCLC and may represent a new immunotherapy target.

BackgroundFever is common in malignant tumors. We report an exceptional case of psychogenic fever in a patient with small cell lung cancer. This is the first case report of psychogenic fever in a patient with small cell lung cancer.Case presentationA 61-year-old Chinese man diagnosed with small cell carcinoma on June 30, 2012, came to our department with a complaint of fever lasting more than 1 month. He had undergone chemoradiotherapy for lung cancer 6 months previously. After admission, his body temperature fluctuated in the range of 37 °C to 39 °C. Somatic symptoms associated with anxiety were obvious. A 24-item Hamilton Anxiety Scale was used to assess the patient’s condition. A score of 32 confirmed a diagnosis of severe anxiety. After a week of antianxiety treatment, the patient’s temperature returned to normal.ConclusionPsychogenic fever is common in cancer patients and deserves more attention. Patients with psychogenic fever must be distinguished from patients with infectious fever (including neutropenic fever), and tumor fever. Additionally, antianxiety or antidepression treatment should be provided. A concern is that continual anxiety may adversely affect anticancer therapy.

Background and objectiveSmall cell lung cancer (SCLC) is the most aggressive type of lung carcinoma with high metastatic potential and chemoresistance upon relapse. Cancer cells remodel the existing metabolic pathways for their benefits and the perturbations in cellular metabolism are the hallmark of cancer. However, the extent of these changes remains largely unknown for SCLC.Materials and methodsWe characterized the metabolic perturbations in SCLC cells (SCLCC) by metabolomics. Large-scale correlation analysis was performed between metabolites. Targeted proteomics and gene expression analysis were employed to investigate the changes of key enzymes and genes in the disturbed pathways.ResultsWe found dramatic decrease of metabolite–metabolite correlations in SCLCC compared with normal control cells and non-small cell lung cancer cells. Pathway analysis revealed that the loss of correlations was associated with the alternations of fatty acid oxidation, urea cycle, and purine salvage pathway in SCLCC. Targeted proteomics and gene expression analysis confirmed significant changes of the expression for the key enzymes and genes in the pathways in SCLCC including the upregulation of carbamoyl phosphate synthase 1 (urea cycle) and carnitine palmitoyltransferase 1A (fatty acid oxidation), and the downregulation of hypoxanthine–guanine phosphoribosyltransferase and adenine phosphoribosyltransferase in purine salvage pathway.ConclusionWe demonstrated the loss of metabolite–metabolite correlations in SCLCC associated with the upregulation of fatty acid oxidation and urea cycle and the downregulation of purine salvage pathways. Our findings provide insights into the metabolic reprogramming in SCLCC and highlight the potential therapeutic targets for the treatment of SCLC.