scholarly journals Detection of micrometastases in peripheral blood of non-small cell lung cancer with a refined immunomagnetic nanoparticle enrichment assay

2011 ◽  
pp. 2175 ◽  
Author(s):  
Qing Li ◽  
Qing Li ◽  
Hui Qi ◽  
Han-Xin Zhou ◽  
Chun-Yan Deng ◽  
...  
2020 ◽  
Vol 8 (2) ◽  
pp. e001302
Author(s):  
Suchita Pakkala ◽  
Kristin Higgins ◽  
Zhengjia Chen ◽  
Gabriel Sica ◽  
Conor Steuer ◽  
...  

BackgroundImmune checkpoint blockade (ICB) targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein 4 has achieved modest clinical activity as salvage therapy in relapsed small cell lung cancer (SCLC). We conducted this signal-finding study to assess the efficacy of ICB with or without radiation in relapsed SCLC.MethodsPatients with relapsed SCLC and ≤2 previous lines of therapy were randomized to (1) arm A: durvalumab (D) 1500 mg/tremelimumab (T) 75 mg (intravenously every 4 weeks without stereotactic body radiation therapy (SBRT)) or (2) arm B: immune-sensitizing SBRT to one selected tumor site (9 Gy × 3 fractions) followed by D/T. Treatment continued until progression or a maximum of 12 months. The co-primary endpoints of the study were overall response rate (ORR) and progression-free survival (PFS). We evaluated circulating lymphocyte repertoire in serial peripheral blood samples and tumor infiltrating lymphocytes (TILs) from on-treatment biopsies as pharmacodynamic markers.ResultsEighteen patients were randomized to arms A and B (n=9 each): median age 70 years; 41.2% women. The median PFS and ORR were 2.1 months and 0% in arm A and 3.3 months and 28.6% in arm B. The median overall survival (OS) was 2.8 months in arm A and 5.7 months in arm B (p=0.3772). Pooled efficacy of D/T±SBRT in 15 Response evaluation criteria in solid tumors (RECIST) evaluable patients across both arms showed the best ORR in terms of partial response in 13.3%, stable disease in 26.6% and progressive disease in 60.0%; the overall median PFS and OS were 2.76 and 3.9 months. The most common adverse events were grade 1 fatigue (66%) and grade 1 elevated amylase (56%) in arm A, and grade 1 fatigue (56%) and pain (44%) in arm B. There was a significant increase in activated CD8(+)ICOS+ T cells (p=0.048) and a reduction in naïve T cells (p=0.0454) in peripheral blood following treatment, along with a significant amount of activated CD8+ICOS+ T cells in TILs from responders.ConclusionsThe D/T combination with and without SBRT was safe but did not show sufficient efficacy signal in relapsed SCLC. Changes in peripheral blood lymphocyte and TILs were consistent with an immunologic response.Trial registration numberNCT02701400.


2020 ◽  
Vol 11 (11) ◽  
pp. 3234-3242
Author(s):  
Wei‐Ran Liu ◽  
Bin Zhang ◽  
Chen Chen ◽  
Yue Li ◽  
Xin Ye ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (35) ◽  
pp. 56233-56240 ◽  
Author(s):  
Hong Zheng ◽  
Xin Liu ◽  
Jianhong Zhang ◽  
Shawn J. Rice ◽  
Matthias Wagman ◽  
...  

2018 ◽  
Vol 47 (6) ◽  
pp. 2407-2419 ◽  
Author(s):  
Hong-Min Wang ◽  
Xiao-Hong Zhang ◽  
Ming-Ming Feng ◽  
Yan-Jun Qiao ◽  
Li-Qun Ye ◽  
...  

Background/Aims: Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease. Methods: A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines. Results: IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions. Conclusion: The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Ning An ◽  
Haoyi Wang ◽  
Wenxiao Jia ◽  
Wang Jing ◽  
Chao Liu ◽  
...  

Abstract Background Immunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression. Methods This study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. The percentages and proliferation potential of T lymphocyte subpopulations from peripheral blood were measured. Results CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) were elevated in ED-SCLC patients compared with healthy controls (p = 0.0083). In contrast, the percentages of CD3+ and CD3+CD4+ T cells were significantly lower in SCLC patients (p < 0.001; p = 0.0014). The proliferation (%divided) of CD8+ T cells of SCLC patients was suppressed compared with healthy controls (p = 0.0058), but not of CD4+ T cells (p = 0.1611). Multivariate analyses showed that the %divided of CD8+ T cells is an independent predictor for PFS (HR: 4.342, 95% CI 1.324–14.245; p = 0.015). The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8+ T cells (p = 0.0225, r = − 0.379; p = 0.0003, r = − 0.464). Conclusion The present study indicates that SCLC patients have impaired immunity in peripheral blood, and the proliferation potential of circulating CD8+ T cells is a significant predicator for PFS.


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