scholarly journals Clinical Significance of Serum-derived Exosomal PD-L1 in Patients with Resected Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Yoshihisa Shimada ◽  
Jun Matsubayashi ◽  
Yujin Kudo ◽  
Sachio Maehara ◽  
Susumu Takeuchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Stage I ◽  
Clinical Activity ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Initial Surgery

Abstract PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8 + tumor-infiltrating lymphocytes (CD8 + TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome's surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8 + TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I-III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8 + TILs (p = 0.001). Patients with serum exosomal PD-L1 ≥ 200 pg/mL tended to have a worse RFS than those with < 200 pg/mL in stage I patients (p = 0.056). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment, 75% of patients with ≥ 200 pg/mL demonstrated a significant response to PD-1 inhibitors. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and be used to assess clinical outcomes in patients with NSCLC.

scholarly journals Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshihisa Shimada ◽  
Jun Matsubayashi ◽  
Yujin Kudo ◽  
Sachio Maehara ◽  
Susumu Takeuchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Stage I ◽  
Clinical Activity ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Initial Surgery

AbstractPD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome’s surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I–III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8+ TILs (p = 0.001). Patients with exosomal PD-L1 ≥ 166 pg/mL tended to have a worse RFS than those with < 166 pg/mL in all stage (p = 0.163) and stage I patients (p = 0.116). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment. The disease control rate of patients with exosomal PD-L1 ≥ 166 pg/mL was 100%. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and clinical outcomes in patients with NSCLC.

scholarly journals Preoperative nivolumab to evaluate pathological response in patients with stage I non-small cell lung cancer: a study protocol of phase II trial (POTENTIAL)

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e043234
Author(s):  
Atsushi Kagimoto ◽  
Yasuhiro Tsutani ◽  
Takahiro Mimae ◽  
Yoshihiro Miyata ◽  
Norihiko Ikeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Small Cell ◽  
Pathological Response ◽  
Stage I ◽  
Small Cell Lung

IntroductionRecently, inhibition of programmed cell death 1 or its ligand has shown therapeutic effects on non-small cell lung cancer (NSCLC). However, the effectiveness of preoperative nivolumab monotherapy for stage I NSCLC remains unknown. The present study aimed to investigate the pathological response of preoperative treatment with nivolumab for clinically node negative but having a high risk of NSCLC recurrence.Methods and analysisThe Preoperative Nivolumab (Opdivo) to evaluate pathologic response in patients with stage I non-small cell lung cancer: a phase 2 trial (POTENTIAL) study is a multicentre phase II trial investigating efficacy of preoperative nivolumab for clinical stage I patients at high risk of recurrence. This study includes histologically or cytologically confirmed NSCLC patients with clinical N0 who were found on preoperative high-resolution CT to have a pure solid tumour without a ground-glass opacity component (clinical T1b, T1c or T2a) or a solid component measuring 2–4 cm in size (clinical T1c or T2a). Patients with epidermal growth factor receptor (EGFR) mutation (deletion of exon 19 or point mutation on exon21, L858R), anaplastic lymphoma kinase (ALK) translocation or c-ros oncogene 1 (ROS-1) translocation are excluded from this study. Nivolumab (240 mg/body) is administrated intravenously as preoperative therapy every 2 weeks for three cycles. Afterward, lobectomy and mediastinal lymph node dissection (ND 2a-1 or ND 2a-2) are performed. The primary endpoint is a pathological complete response in the resected specimens. The secondary endpoints are safety, response rates and major pathological response. The planed sample size is 50 patients. Patients have been enrolled since April 2019.Ethics and disseminationThis trial was approved by the Institutional Review Board of Hiroshima University Hospital and other participating institutions. This trial will help examine the efficacy of preoperative nivolumab therapy for clinical stage I NSCLC.Trial registration numberjRCT2061180016.

scholarly journals Metabolic Changes in Early-Stage Non–Small Cell Lung Cancer Patients after Surgical Resection

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3012
Author(s):  
Naseer Ahmed ◽  
Biniam Kidane ◽  
Le Wang ◽  
Zoann Nugent ◽  
Nataliya Moldovan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Surgical Resection ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Resonance Spectroscopy ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Post Surgery

Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals Tumor cellular proliferation is associated with enhanced immune checkpoint expression in stage I non–small cell lung cancer

2019 ◽  
Vol 158 (3) ◽  
pp. 911-919.e6 ◽  
Author(s):  
Kyle G. Mitchell ◽  
Edwin R. Parra ◽  
David B. Nelson ◽  
Jiexin Zhang ◽  
Ignacio I. Wistuba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Cellular Proliferation ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung
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