OA12.04 Pre-Treatment T-Cell Receptors (TCR) Repertoire in Non-Small Cell Lung Cancer (NSCLC) Patients Treated With Single Agent Immunotherapy

2021 ◽  
Vol 16 (10) ◽  
pp. S870
Author(s):  
A. Abed ◽  
L. Calapre ◽  
S. Bowyer ◽  
M. Millward ◽  
E. Gray
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
T Cell Receptors ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tcr Repertoire ◽  
Pre Treatment ◽  
Nsclc Patients

scholarly journals Deep Sequencing of T-Cell Receptors for Monitoring Peripheral CD8+ T Cells in Chinese Advanced Non–Small-Cell Lung Cancer Patients Treated With the Anti–PD-L1 Antibody

2021 ◽  
Vol 8 ◽  
Author(s):  
Jin Sheng ◽  
Huadi Wang ◽  
Xiao Liu ◽  
Yunyun Deng ◽  
Yingying Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Deep Sequencing ◽  
T Cell Receptors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tcr Repertoire ◽  
Response Group ◽  
Nsclc Patients

Background: Atezolizumab, a high-affinity engineered human anti–PD-L1 antibody, has produced a clinical benefit for patients with advanced non–small-cell lung cancer (NSCLC). However, associated with T-cell regulation, the immunomodulatory effect of PD-L1 blockade and its biomarker in peripheral immunity remains elusive.Methods: In a prospective cohort with 12 Chinese advanced NSCLC patients who received atezolizumab 1,200 mg every 3 weeks as a second-line treatment, blood samples were obtained before and 6 weeks after atezolizumab initiation, and when disease progression was confirmed. Patients were classified into a response or progression group according to response evaluation criteria in solid tumors (RECIST) 1.1. Fresh peripheral blood mononuclear cells (PBMCs) from patients were stained with antihuman CD3, CD8, and PD-1 antibodies for flow cytometry analysis. T-cell receptor (TCR)-β chains of CD8+ T cells were analyzed by next-generation sequencing (NGS) at the deep level. Diversity, clonality, and similarity of TCR have been calculated before and after treatment in both groups.Results: Clonal expansion with high PD-1 expression was detected in all patients’ peripheral CD8+ T cells before the treatment of atezolizumab. Unlike the progression group, the diversity of TCR repertoire and singletons in the TCRβ pool increased over time with atezolizumab administration, and the TCR repertoire dynamically changes in the response group. The percentage of CD8+ PD-1high terminal exhausted T cells declined in the response group after the PD-L1 blockade. Two patterns of TCR changes among patients who received PD-L1–targeted immunotherapy were observed.Conclusions: Deep sequencing of the T-cell receptors confirmed the existence of CD8+ PD-1high T cells with an exhaustion phenotype in Chinese NSCLC patients. Our study demonstrated that efficient anti–PD-L1 therapy could reshape the TCR repertoire for antitumor patients. Furthermore, singleton frequency may help us select patients who are sensitive to anti–PD-L1 immunotherapy.

scholarly journals Vinorelbine in Non-Small Cell Lung Cancer: Real-World Data From a Single-Institution Experience

2020 ◽  
Vol 28 (3) ◽  
pp. 237-248
Author(s):  
Stefania Nobili ◽  
Daniele Lavacchi ◽  
Gabriele Perrone ◽  
Giulio Vicini ◽  
Renato Tassi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Institution ◽  
Nsclc Patients ◽  
Combination Regimens

The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician’s choice; 61.7% were older than 70 years, and 60.5% were affected by ≥2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p = 0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or ≤2 metastatic lesions. Grade 3‐4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jianming Hu ◽  
Jiawei Hu ◽  
Xiaolan Liu ◽  
Long Li ◽  
Xue Bai
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

Circulating biomarkers and outcomes in advanced non-small cell lung cancer patients treated with anti-PD1 (program death 1 receptor) monoclonal antibodies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20592-e20592
Author(s):  
Mary J. Fidler ◽  
Marta Batus ◽  
Imad Tarhoni ◽  
Selina Sayidine ◽  
Cristina L. Fhied ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
T Cell ◽  
Pilot Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e20592 Background: Current evaluation of immunohistochemical expression of PDL-1 (program death receptor 1 ligand) can select some non-small cell lung cancer (NSCLC) patients who may benefit from anti-PD1 directed therapy. It is an imperfect marker and there is little information about systemic modulation of the immune system on therapy. In this study we explored the prognostic value of baseline circulating immune checkpoint and inflammatory molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD1 therapy. Methods: Prospectively collected serum from advanced NSCLC patients receiving nivolumab or pembrolizumab were evaluated with the MILLIPLEX Human High Sensitivity T-cell (17-plex) and ProcartaPlex Human Immuno-Oncology Checkpoint (14-plex) panels on our Luminex FlexMAP 3D. Biomarker level cutoffs were optimized and evaluated against progression-free survival (PFS) and overall survival (OS) using log-rank analysis. Results: 21 cases were enrolled in this pilot study: 72% Caucasian, 61% female, 24% never-smokers. IL-10 was found to have a significant association with both PFS (p = 0.0055) and OS (p = 0.024), with levels below 3.32 pg/mL being associated with a superior clinical outcome. We also found IL-2 and IL-6 to have significant associations with PFS (p = 0.033 and 0.040, respectively), again, with low levels being associated with a superior outcome. Neither of these had significant associations with OS. Low circulating levels of the T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) protein were associated with superior PFS (p = 0.036), and a weak trend (p = 0.19) for OS. Conclusions: In this small exploratory pilot study we identified several circulating molecules associated with inflammation and immune system regulation that may have prognostic value for anti-PD-1 therapy. Notably, TIM-3 is a Th1-specific protein associated with macrophage activation and is also a component of T-cell exhaustion along with LAG3 and PD-1. Additional studies to follow up on these findings in larger cohorts are underway.

scholarly journals T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Lirong Wu ◽  
Jun Zhu ◽  
Nils-Petter Rudqvist ◽  
James Welsh ◽  
Percy Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
T Cell Receptor ◽  
Shannon Entropy ◽  
Cell Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tcr Repertoire ◽  
Before And After

Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure after SBRT. TCR repertoires were analyzed in peripheral blood mononuclear cells (PBMCs) collected before and after SBRT from 19 patients. TCR combinational diversity in V and J genes was assessed with multiplex PCR of genomic DNA from PBMCs and tested for associations with clinical response. All patients received definitive SBRT to a biologically effective dose of >=100 Gy. The number of unique TCR clones was decreased after SBRT versus before, but clonality and the Shannon Entropy did not change. Four patients (21%) developed distant metastases after SBRT (median 7 months); those patients had lower Shannon Entropy in post-SBRT samples than patients without metastasis. Patients with a low change in Shannon Entropy from before to after SBRT [(post-SBRT Shannon Entropy minus baseline Shannon)/(baseline Shannon) * 100] had poorer metastasis-free survival than those with high change in Shannon Entropy (P<0.001). Frequencies in V/J gene fragment expression in the TCR β chain were also different for patients with or without metastases (two V fragments in baseline samples and 2 J and 9 V fragments in post-treatment samples). This comprehensive analysis of immune status before and after SBRT showed that quantitative assessments of TCRs can help evaluate prognosis in early-stage NSCLC.

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