scholarly journals P3.02c-103 Effect of Anti-PD-1 Therapy on Immune Cells in the Peripheral Blood of Non-Small Cell Lung Cancer (NSCLC) Patients

2017 ◽  
Vol 12 (1) ◽  
pp. S1342-S1343
Author(s):  
Eleni- Kyriaki Vetsika ◽  
Despoina Aggouraki ◽  
Zacharoula Lyristi ◽  
Filippos Koinis ◽  
Vassilis Georgoulias ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

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 Decreased IL-27 Negatively Correlated with Th17 Cells in Non-Small-Cell Lung Cancer Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Minchao Duan ◽  
Zhengqing Ning ◽  
Zhijun Fu ◽  
Jianquan Zhang ◽  
Guangnan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Small Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Small Cell Lung ◽  
Nsclc Patients

The presence of Th17 cells and IL-27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL-27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL-27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL-27 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL-27 in the peripheral blood was examined by real-time quantitative polymerase chain reaction (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL-17 and RORγt. IL-27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL-27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.

Longitudinal sequencing of TCR and circulating tumor DNA revealing radiotherapeutic efficacy and prognosis for non-small cell lung cancer patients with brain metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21181-e21181
Author(s):  
Xiaorong Dong ◽  
Lingjuan Chen ◽  
Fan Tong ◽  
Chunhua Wei ◽  
Han Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
High Throughput Sequencing ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tcr Diversity ◽  
Nsclc Patients

e21181 Background: This study aimed to explore cerebrospinal fluid (CSF) and peripheral blood-based liquid biopsy before and after radiotherapy of non-small cell lung cancer (NSCLC) brain metastases. Methods: Thirty NSCLC patients with brain metastases receiving brain radiotherapy were enrolled in this study. CSF and peripheral blood were collected at baseline, 24 hours (T0) and 28 days (T28) after treatment. Somatic mutations and T-cell receptor (TCR) sequences were identified by high-throughput sequencing in both compartments. Results: At baseline, identical mutations shared by paired blood and CSF emerged in nine patients (30%). Dimension reduction analysis identified distinct signatures of V and J gene recombination in blood and CSF TCR sequences. Throughout treatment, both compartments experienced a TCR diversity decrease, however, the degradation of low-abundance clones and the expansion of emerging clones might be two separate processes underwent in blood and CSF, respectively. Diversity changes and ctDNA in blood were possibly related to pulmonary responses, while the increase of maximal clone abundance in CSF might indicate a favorable intracranial response. Blood-ctDNA clearance at T28 was significantly associated with better overall survival (OS, HR = 4.027, p = 0.028) and progression-free survival (PFS, HR = 4.176, p = 0.024), and superior blood TCR diversity at T28 against baseline was associated with longer OS (HR = 5.700, p = 0.039). Combined blood factors achieved a better predictive power (OS, HR = 10.53, p < 0.001; PFS, HR = 4.843, p < 0.001). Patients with increase of maximal clone abundance ≥ 50 in CSF also had a better intracranial PFS (HR = 8.320, p = 0.011). The predictive effects of these markers were independent of other clinical factors in multivariate Cox analysis. Conclusions: CSF and peripheral blood were independent compartments showing disparate genomic and immune signatures. Longitudinal surveillance of both compartments could be a promising method to predict clinical outcomes for NSCLC patients with brain metastases.

Peripheral blood biomarkers associated with outcome in non-small cell lung cancer patients treated with nivolumab and durvalumab monotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21732-e21732
Author(s):  
Lin Wu ◽  
Meilin Jiang ◽  
Wenying Peng ◽  
Xingxiang Pu ◽  
Bolin Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Nsclc Patients

e21732 Background: Selecting patients that potentially benefit from immune checkpoint inhibitors (ICIs) is critical. Programmed death ligand-1 (PD-L1) protein immunohistochemical expression on cancer cells or immune cells and Next generation sequencing based tumor mutational burden (TMB) are the hot spots in studies on ICIs, but there is still confusion in the testing methods. Due to blood samples are much easier for clinical application, many potential peripheral biomarkers have been proposed. This study identify blood parameters that associated with outcome of non-small cell lung cancer (NSCLC) patients with ICIs monotherapy. Methods: Data of 76 NSCLC patients were analyzed retrospectively. To assess the connection between survival and peripheral blood markers measured before and after treatment, we utilized COX regression model survival analysis and receiver operating characteristic (ROC) curve to assess the markers. Results: In the nivolumab cohort, the optimal cutoff for predicting 11 month overall survival (OS) were 168.13 and 43g/L in Plateletto-lymphocyte ratio (PLR) and albumin, respectively. When patients are grouped with PLR and albumin the cut-offs, a significant difference in SD-PR vursus PD rate were found between high and low groups, separately. which was not found when grouped by PD-L1 expression. Patients with high PLR ( > 168.13) or low albumin ( < = 43g/L) before ICI had a significantly raised hazard of progression, separately (for PLR, P = 0.006; for albumin, P = 0.033) and of death (for PLR, P = 0.014; for albumin, P = 0.009) compared with those patients who had low PLR or albumin level. More importantly, we found that higher PLR ( > 168.13) after the fourth cycle of ICIs was also an prognostic biomarker, which significantly correlated with shorter OS in both Nivolumab (P = 0.046) and durvalumab cohort (P = 0.028). Conclusions: PLR and albumin may help the stratification of high progression and death risk group in advanced NSCLC patients treated with nivolumab and durvalumab monotherapy.

Abstract 619: Effect of anti-PD-1 therapy on immune cells in the peripheral blood of non-small cell lung cancer patients

2017 ◽  
Author(s):  
Eleni-Kyriaki Vetsika ◽  
Galatea Kallergi ◽  
Despoina Aggouraki ◽  
Zaharoula Lyristi ◽  
Aristeidis Koukos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

KEAP1/NFE2L2 as a prognostic biomarker on immunotherapy and correlation with immune infiltrates in non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21551-e21551
Author(s):  
Hongyuan Zhu ◽  
Yunfang Yu ◽  
Yating Zheng ◽  
Bin Xu ◽  
Shaopeng Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cells ◽  
Small Cell ◽  
Study Cohort ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Nsclc Patients

e21551 Background: Molecular characterization studies revealed recurrent KEAP1/ NFE2L2 alterations in non-small cell lung cancer (NSCLC). Previous studies have confirmed that KEAP1/NFE2L2 mutations are a poor prognostic factor for chemotherapy in patients with NSCLC. Nevertheless, it is unclear whether KEAP1/NFE2L2 mutations (MUT) of liquid biopsy can predict the efficacy of immunotherapy in NSCLC. Methods: Two independent cohorts (the OAK and POPLAR study cohort) with data from approximately 853 patients with advanced NSCLC were used to analyze the prognostic effect of KEAP1/NFE2L2 on immunotherapy. In addition, based on a deconvolution algorithm (known as CIBERSORT), we comprehensively analyzed the tumor-infiltrating immune cells present in NSCLC. The fraction of 22 immune cells subpopulations was evaluated to determine the associations between each cell type and KEAP1/NFE2L2 mutation status utilizing data from 1268 patients by lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) in TCGA pan-cancer cohort. Results: The OAK and POPLAR study cohort of NSCLC patients showed that KEAP1/NFE2L2 MUT was associated with poorer overall survival (OS), and progression-free survival (PFS) (OS: HR = 1.7, P < 0.001; PFS:HR = 1.4, P < 0.001) on immunotherapy, even after EGFR and ALK mutations were excluded, significant difference can also be gained (OS:HR = 1.8, P < 0.001; PFS:HR = 1.5, P < 0.001). Then, the NSCLC patients were subdivided into LUAD and LUSC, the OS and PFS of patients with KEAP1/NFE2L2 MUT is lower than wild-type (WT) (OS:HR = 1.8, P < 0.001; PFS:HR = 1.4, P = 0.0014) in LUAD, significant differences were obtained even when EGFR and ALK mutations were excluded (OS:HR = 1.9, P < 0.001;PFS:HR = 1.6, P < 0.001). In LUSC, patients with KEAP1/NFE2L2 MUT have lower OS (HR = 1.4, P = 0.0473),and there was no difference on PFS (HR = 1.2, P = 0.1588) between KEAP1/NFE2L2 MUT and WT, when EGFR and ALK mutations were excluded, the survival results did not change significantly. In addition, KEAP1/NFE2L2 MUT was positively correlated with infiltrating levels of plasma cells, T cells CD4 memory activated, T cells follicular helper, and Macrophages M1, but negatively correlated with infiltrating levels of T cells CD4 memory resting, monocytes, Dendritic cells activated, Mast cells resting, and Neutrophils in NSCLC. The immunoinfiltration of LUAD was significantly different from that of LUSC. Conclusions: These findings suggest that KEAP1/NFE2L2 can be used as a poorer biomarker for determining prognosis on immunotherapy and immune infiltration in NSCLC.

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