scholarly journals Expression of PD-1 on CD4+ T cells in peripheral blood associates with poor clinical outcome in non-small cell lung cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (35) ◽  
pp. 56233-56240 ◽  
Author(s):  
Hong Zheng ◽  
Xin Liu ◽  
Jianhong Zhang ◽  
Shawn J. Rice ◽  
Matthias Wagman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Poor Clinical Outcome

scholarly journals Interleukin-35 Suppresses the Antitumor Activity of T Cells in Patients with Non-Small Cell Lung Cancer

2018 ◽  
Vol 47 (6) ◽  
pp. 2407-2419 ◽  
Author(s):  
Hong-Min Wang ◽  
Xiao-Hong Zhang ◽  
Ming-Ming Feng ◽  
Yan-Jun Qiao ◽  
Li-Qun Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

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.

scholarly journals Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study

2020 ◽  
Vol 8 (2) ◽  
pp. e001302
Author(s):  
Suchita Pakkala ◽  
Kristin Higgins ◽  
Zhengjia Chen ◽  
Gabriel Sica ◽  
Conor Steuer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Radiation Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Stereotactic Body Radiation Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stereotactic Body Radiation

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.

scholarly journals The prognostic role of circulating CD8+ T cell proliferation in patients with untreated extensive stage small cell lung cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Ning An ◽  
Haoyi Wang ◽  
Wenxiao Jia ◽  
Wang Jing ◽  
Chao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
T Lymphocyte ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Small Cell ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Proliferation Potential

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.

scholarly journals Single-cell Profiling of Immune cells After Neoadjuvant Pembrolizumab and Chemotherapy in ⅢA non-small cell lung cancer (NSCLC)

2021 ◽  
Author(s):  
Xiubao Ren ◽  
Zhenzhen Hui ◽  
Jiali Zhang ◽  
Yulin Ren ◽  
XIAOLING LI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Single Cell ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Responses

Abstract The combination of immune checkpoint inhibitors (ICIs) with chemotherapy (chemoimmunotherapy) in the neoadjuvant setting have achieved favorable clinical benefits in non-small cell lung cancer (NSCLC), but the mechanism of clinical responses remain unclear. To identify factors associated with the clinical outcome, we provide a rich resource of 186,477 individual immune cells from matched multiple immune-relevant tissue sites and peripheral blood of four treatment-naïve and eight neoadjuvant chemoimmunotherapy treated ⅢA NSCLC patients (responders versus non-responders) by single-cell RNA-seq and TCR-seq. We showed that the synergistic increase of B cells and CD4+ T cells are associated with positive therapeutic response of neoadjuvant chemoimmunotherapy. B cell IgG subclasses IgG1 and IgG3 play a critical role in anti-tumor immune response in tumor lesion, and this process was driven by increased IL-21 protein secreted by infiltrated T follicular helper (Tfh) cells after neoadjuvant chemoimmunotherapy. Furthermore, we uncovered several critical events for positive clinical outcome, including the diminished activated TNFRSF4+ regulatory T cells (Tregs), increased LAMP3+ dendritic cells (DCs), high pre-therapy peripheral blood T-cell diversity, and the expansion of intratumoral CD4+ T clones and peripheral CD8+ T clones. In total, our comprehensive study of the single-cell profile of immune cells provide mechanistic insight of clinical responses and identified novel predictive factors and potential therapeutic targets for improving the efficiency of neoadjuvant chemoimmunotherapy in NSCLC.

PD-L1+CD4+ T cells and soluble PD-L1 as prognostic factors to anti-PD-1 immunotherapy in advanced non small cell lung cancer patients.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24091-e24091
Author(s):  
EleniKyriaki Vetsika ◽  
Despoina Aggouraki ◽  
Zacharoula Lyristi ◽  
Aristeidis Koukos ◽  
Despoina Kourougkiaouri ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Cd4 T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients
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