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.

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.

Impact of EGFR and ALK mutation on the outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 2005-2005 ◽  
Author(s):  
Suresh Kumar Balasubramanian ◽  
Vyshak Alva Venur ◽  
Samuel T. Chao ◽  
Lilyana Angelov ◽  
Alireza Mohammad Mohammadi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

scholarly journals P14.97 High risk of venous thromboembolism in patients with brain metastases from non-small cell lung cancer

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii91-iii91
Author(s):  
P Mir Seyed Nazari ◽  
C Ay ◽  
A Steindl ◽  
B Gatterbauer ◽  
J M Frischer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract BACKGROUND Venous thromboembolism (VTE) is a common complication in patients with cancer. In general, patients with metastatic disease are at highest risk. Lung cancer belong to those tumor entities with a particularly high risk of VTE, ranging between 3–13.8%. However, little is known about the VTE rate in lung cancer patients with brain metastases. MATERIAL AND METHODS Our study was conducted in the framework of the Vienna Brain Metastasis Registry. Clinical data and VTE events during the course of the disease were recorded via retrospective chart review. In this analysis, non-small cell lung cancer (NSCLC) patients with a resection of brain metastases at the Medical University of Vienna between 2006 and 2010 were included. RESULTS In total, 69 NSCLC patients with brain metastases were analyzed. Overall, 69.6% (48/69) patients had an adenocarcinoma, 13% (9/69) a squamous cell carcinoma, 8.7% (6/69) a large cell carcinoma and 8.7% (6/69) other primary tumor histologies. After cancer diagnosis, 20.3% (14/69) patients developed VTE during the course of the disease. Of those, 85.7% (12/14) thromboembolic events occurred after the diagnosis of brain metastases. CONCLUSION Based on our data, patients with brain metastases from NSCLC have a very high VTE risk. Further investigations are needed in order to identify patients with distinct VTE risk profiles. Patients at high risk might potentially benefit from primary thromboprophylaxis over the high risk of intracerebral bleeding.

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 Alectinib Treatment of ALK Positive Non Small Cell Lung Cancer Patients with Brain Metastases: Our Clinical Experience

PRILOZI ◽  
2020 ◽  
Vol 41 (2) ◽  
pp. 29-36
Author(s):  
Simonida Crvenkova
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Performance Status ◽  
Small Cell ◽  
Poor Performance Status ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Nsclc Patients

AbstractSummary: Anaplastic lymphoma kinase (ALK) rearrangement is identified in approximately 3-7% of all metastatic non-small cell lung cancer (NSCLC) patients, and ALK tyrosine kinase inhibitors (TKIs) have revolutionized the management of this subset of lung cancer cases.Purpose: This study aims to show alectinib (TKI) effectiveness and safety with focus on alectinib intracranial efficacy for ALK+ NSCLC patients.Case presentation: Patient 1 was a 46-year-old woman diagnosed with non-small cell lung cancer with an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene (ALK+). She presented with intracranial and liver metastases and poor performance status of ECOG 3. Alectinib was initiated as a second line therapy, after whole brain irradiation and discontinuation of first line chemotherapy after two cycles, due to the central nervous system progression and liver metastases. Good response was consequently achieved, characterized with improved overall performance and without significant adverse events.Patient 2 was a 53-year old man with left sided lung adenocarcinoma surgically treated in 2017. Post-operative pTNM stage was IIB with a positive resection margin- R1. He received adjuvant chemotherapy and radiotherapy. In 2019, after two and half years of being disease free, he presented with severe cerebral symptoms leading to poor performance status. CT scan of the brain showed multiple brain metastases. He was treated with first line alectinib after completion of whole brain radiotherapy. In 5 months period he got significantly better and able for work again.Conclusions: We recommend alectinib as a first and second line treatment approach for ALK+ NSCLC patients, in particular the ones with brain metastases at the time of diagnosis and poor PS.

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