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Background: The aim of this study was to evaluate the safety and survival outcomes of anti-programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) monotherapy in patients with advanced nonsmall cell lung cancer (NSCLC) and different hepatitis B virus (HBV) infection status. Methods: Patients with advanced NSCLC and both chronic and/or resolved HBV infection who were treated with anti-PD-(L)1 monotherapy were retrospectively enrolled. The primary endpoint was the safety of PD-1/PD-L1 monotherapy, while the secondary endpoints included the survival outcomes. Results: Of the 62 eligible patients, 10 (16.1%) were hepatitis B surface antigen (HBsAg) positive [chronic hepatitis B (CHB) infection] and 52 (83.9%) were HBsAg negative and HBcAb positive [resolved hepatitis B (RHB) infection]; 42 (67.7%) patients had at least 1 treatment-related adverse event (AE), with 4 patients (6.5%) developing grade 3 AEs and 6 (9.7%) developing hepatic AEs. One CHB patient experienced HBV reactivation during anti-PD-1 immunotherapy due to the interruption of antiviral prophylaxis. The objective response rate and durable clinical benefit (DCB) rate were 17.7% and 29.0%, respectively. Median overall survival (OS) and progression-free survival (PFS) were 23.6 months [95% confidence interval (CI): 14.432.8] and 2.1 months (95% CI: 1.2-3.0), respectively. The DCB rate was significantly higher in the CHB group than in the RHB group (60% vs. 23.1%; P=0.048). Patients with CHB experienced a longer PFS (8.3 vs. 2.0 months; P=0.103) and OS (35.0 vs. 18.2 months, P=0.119) than did RHB patients. Conclusions: Anti-PD-(L)1 monotherapy was safe and effective in patients with NSCLC and HBV infection. This population should not be excluded from receiving immunotherapy in routine clinical practice or within clinical trials if HBV biomarkers are monitored and antiviral prophylaxis is properly used.

Background The aim of the present study was to analyze the association of programmed cell death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) expression levels with clinicopathological characteristics and survival to provide a treatment strategy for rectal cancer. Methods Immunohistochemical staining of VEGFR2 and PD-L1 was carried out, and the association of PD-L1 and VEGFR2 expression levels with clinicopathological characteristics and survival were investigated in 77 pair-matched rectal cancer patients. Results PD-L1 and VEGFR2 expression levels in surgical tumor tissues were higher than those in paired adjacent normal tissues, respectively (both P

Background: Lung cancer is the most frequent cause of cancer-related deaths worldwide. The clinical development of immune checkpoint blockade has dramatically changed the treatment paradigm for patients with lung cancer. Yet, an improved understanding of PD-1/PD-L1 checkpoint blockade-responsive biology is warranted. Methods: We aimed to identify the landscape of immune cell infiltration in primary lung adenocarcinoma (LUAD) in the context of tumoral PD-L1 expression and the extent of immune infiltration (“hot” vs. “cold” phenotype). The study comprises LUAD cases (n = 138) with “hot” (≥150 lymphocytes/HPF) and “cold” (&lt, 150 lymphocytes/HPF) tumor immune phenotype and positive (&gt, 50%) and negative (&lt, 1%) tumor PD-L1 expression, respectively. Tumor samples were immunohistochemically analyzed for expression of PD-L1, CD4, and CD8, and further investigated by transcriptome analysis. Results: Gene set enrichment analysis defined complement, IL-JAK-STAT signaling, KRAS signaling, inflammatory response, TNF-alpha signaling, interferon-gamma response, interferon-alpha response, and allograft rejection as significantly upregulated pathways in the PD-L1-positive hot subgroup. Additionally, we demonstrated that STAT1 is upregulated in the PD-L1-positive hot subgroup and KIT in the PD-L1-negative hot subgroup. Conclusion: The presented study illustrates novel aspects of PD-L1 regulation, with potential biological relevance, as well as relevance for immunotherapy response stratification.

BackgroundStudies investigating the correlation between the expression of programmed cell death-ligand 1 (PD-L1) and prognosis in patients with esophageal squamous cell carcinoma (ESCC) not receiving preoperative therapy have increased significantly, but conclusions remain inconclusive. Therefore, this study aimed to determine the association between clinical outcomes and expression of PD-L1 in ESCC patients without preoperative therapy.MethodsWe conducted a comprehensive literature search using four databases up to May 2020. Quality assessment was carried out according to the Newcastle–Ottawa Quality Assessment Scale (NOS). Hazard ratios (HRs) were used to analyze the association between PD-L1 expression with prognosis. Furthermore, we evaluated the correlation between PD-L1 and clinicopathological characteristics using odds ratios (ORs) and 95% confidence intervals (CIs).ResultsTwenty studies (19 publications) comprising 3,677 patients were included in this meta-analysis. We found that the expression of PD-L1 was not related to overall survival (OS, HR: 1.16, 95% CI: 0.94–1.42, p = 0.16) or disease-free survival (DFS, HR: 0.85, 95% CI: 0.66–1.10, p = 0.21) in ESCC. Furthermore, although PD-L1 expression was not significantly associated with sex, degree of differentiation, TNM stage, T stage, lymph node status, smoking, or alcohol use, the merged OR demonstrated that the expression of PD-L1 was higher in older patients compared to younger patients (OR: 1.40, 95% CI: 1.07–1.83, p = 0.01). No obvious publication bias was observed.ConclusionsOur present study illustrated that PD-L1 expression was not related to poor prognosis of ESCC patients not receiving preoperative therapy, albeit the association only showed a tendency for statistical significance. Notably, PD−L1 expression showed a significant association with age. This meta-analysis had several limitations; therefore, our results need to be verified through further large-scale and prospective studies.

To better understand the etiology of inflammatory breast cancer (IBC) and identify potential therapies, we studied genomic alterations in IBC patients. Targeted, next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) (n = 33) and paired DNA from tumor tissues (n = 29) from 32 IBC patients. We confirmed complementarity between cfDNA and tumor tissue genetic profiles. We found a high incidence of germline variants in IBC patients that could be associated with an increased risk of developing the disease. Furthermore, 31% of IBC patients showed deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We also characterized the tumor-infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1, and PD-L1) through immunohistochemistry (IHC) staining. In 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs, making them sensitive to PD-1/PD-L1 blocking therapies. Our results provide a rationale for considering PARP inhibitors and PD-1/PDL1 blocking immunotherapy in qualifying IBC patients.

BackgroundAtezolizumab plus chemotherapy has been recommended as a first-line treatment option for patients with advanced non-small cell lung carcinoma (NSCLC) irrespective of programmed cell death-ligand 1 (PD-L1) expression. Currently, little is known about the efficacy and treatment-related adverse effects (TRAEs) of subtracting chemotherapy from the combination for patients with high PD-L1 expression. Thus, we performed an indirect comparison between atezolizumab plus chemotherapy and atezolizumab alone.MethodsA total of five eligible randomized controlled trials (RCTs) were identified from PubMed, EMBASE, and Cochrane Central controlled trial registries, using keywords including atezolizumab, PD-1, PD-L1, NSCLC, and RCT. The clinical outcomes of objective response rate (ORR), progression-free survival (PFS), OS, and TRAEs were extracted and evaluated. Using indirect analysis, the efficacy and TRAEs were compared between arm A (atezolizumab plus chemotherapy) and arm C (atezolizumab), linked by arm B (chemotherapy).ResultsDirect comparison revealed that both atezolizumab plus chemotherapy (HR 0.65, P = 0.003) and atezolizumab alone (HR 0.59, P = 0.010) significantly improved OS compared with chemotherapy. More importantly, the indirect comparison showed that atezolizumab plus chemotherapy was not superior to atezolizumab regarding OS (RR 1.10, P =0.695) and ORR (RR 1.11, P = 0.645). However, patients who received atezolizumab combined with chemotherapy experienced more ≥ grade 3 TRAEs (RR 4.23, PPConclusionsAtezolizumab monotherapy might be a better treatment option for patients with advanced NSCLC and high PD-L1 expression than atezolizumab plus chemotherapy.

// Yuko Oya 1 , Tatsuya Yoshida 1 , Hiroaki Kuroda 2 , Masashi Mikubo 3 , Chiaki Kondo 1 , Junichi Shimizu 1 , Yoshitsugu Horio 1 , Yukinori Sakao 2 , Toyoaki Hida 1 and Yasushi Yatabe 3 1 Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan 2 Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan 3 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan Correspondence to: Tatsuya Yoshida, email: t.yoshida@aichi-cc.jp Keywords: nivolumab, non-small cell lung cancer, programmed cell death-1(PD-1), programmed cell death-ligand 1 (PD-L1) Received: June 27, 2017 Accepted: September 21, 2017 Published: October 07, 2017 ABSTRACT Background: Nivolumab offers a superior survival benefit over docetaxel in patients with advanced, previously treated non-small-cell lung cancer (NSCLC). An association between programmed cell death ligand-1 (PD-L1) expression and the efficacy of nivolumab has been reported in many studies. However, the association between the clinical parameters and efficacy of nivolumab remains unclear in advanced NSCLC patients. Results: Among 124 patients, 108 (88%) were performance status (PS) 0 to 1. PD-L1 expression was assessed in 89 patients, with 51 (57%) patients having PD-L1 positive expression. In all patients, the objective response rate (ORR) in patients with elevated CRP levels (≥ 1 mg/dl) was significantly worse than those without elevated CRP levels (< 1 mg/dl) (8.3 vs 23.4%, p = 0.0180). The PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) were significantly associated with a shorter PFS and OS in patients treated with nivolumab. Multivariate analyses showed that the PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) and PD-L1 expression were significant factors associated with a longer PFS of nivolumab. Materials and Methods: We retrospectively analyzed 124 patients who received nivolumab as a subsequent treatment. The patient characteristics, laboratory data at baseline (C-reactive protein [CRP] and lactate dehydrogenase [LDH]), PD-L1 expression, nivolumab response, progression-free survival (PFS), and overall survival (OS) were evaluated. Conclusions: Clinical parameters, such as PS, serum CRP, serum LDH, and smoking status, were significantly associated with the response duration and survival in patients treated with nivolumab.

Background The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis. Methods We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical (IHC) assay. The expression of anaplastic lymphoma kinase (ALK), CD5, CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein–Barr virus (EBV)-encoded RNAs (EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan–Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis. Results Of the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype (P = 0.02 and P = 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment (P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression (r = − 0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival (OS) rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells (P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS (P