Helper T cells in malignant pleural effusion

2021 ◽  
Vol 500 ◽  
pp. 21-28
Author(s):  
Feng-Shuang Yi ◽  
Kan Zhai ◽  
Huan-Zhong Shi
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Malignant Pleural Effusion ◽  
Helper T Cells

Analysis of regulatory T cells in patients of NSCLC with malignant pleural effusion.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17511-e17511
Author(s):  
Prabhat Singh Malik ◽  
Vinod Raina ◽  
Amar Singh ◽  
Dipendrea Kumar Mitra
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Peripheral Blood ◽  
Chemokine Receptors ◽  
Malignant Pleural Effusion ◽  
Advanced Nsclc ◽  
Treg Cells ◽  
Healthy Controls ◽  
Anatomic Site ◽  
Treg Frequency

e17511 Background: Enrichment of regulatory T (Treg) cells at the affected anatomic site in cancer may suppress the anti-tumor immune response influencing the cancer progression. Understanding of the clinical relevance of Treg mediated suppression of anti-tumor immune response and mechanisms underlying their preferential trafficking to the affected anatomic site is still limited. The aim of this study was to enumerate the frequencies of Treg cells in malignant pleural effusion and peripheral blood of patients with advanced NSCLC and it’s trend after treatment. Methods: Treg frequencies were evaluated in pleural effusion and peripheral blood of the patients with advanced NSCLC (n=27) using flowcytometry and compared with peripheral blood of age and sex matched healthy controls (n=15) and tubercular pleural effusions (n=10). The Treg cells were characterized as CD4+CD25+Foxp3+ T cells gated on CD4+CD25+ T cells. We assessed the effect of treatment response on Treg frequency. We have also looked for the expression of chemokine receptors CCR4 and CCR6 on the Tregs in pleural effusion and peripheral blood of the patients. Results: Compared to healthy controls, frequency of CD4+CD25+Foxp3+ Tregs was significantly increased in peripheral blood of patients with NSCLC (p=0.0036). In pleural effusion of patients, Treg frequency was higher than their corresponding peripheral blood (p=0.025). As compared to tubercular pleural effusion Treg frequency was higher in malignant effusion (p<0.0001). We had 12 patients who completed treatment and in whom response evaluation was available. Treg frequency reduced at the time of response (PR or SD) and increased again at disease progression. Surface expression of CCR4 and CCR6 was higher on Treg cells as compared to non Treg CD4 cells among the patients (p=0.0001; p=0.001 respectively). However, there was no difference in expression of these chemokine receptors on Tregs in pleural fluid and peripheral blood. Conclusions: Tregs are increased in patients of NSCLC, both at disease site and in systemic circulation. This increase may be chemokine receptors mediated. Treg frequency changes with treatment and response. Modulation of Tregs may have therapeutic implication in the management of advanced NSCLC.

scholarly journals Polarized helper T cells in tubercular pleural effusion: phenotypic identity and selective recruitment

2005 ◽  
Vol 35 (8) ◽  
pp. 2367-2375 ◽  
Author(s):  
Dipendra K. Mitra ◽  
Surendra K. Sharma ◽  
Amit K. Dinda ◽  
Manjit S. Bindra ◽  
Babita Madan ◽  
...  
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Helper T Cells

scholarly journals Generation and Differentiation of IL-17–Producing CD4+ T Cells in Malignant Pleural Effusion

2010 ◽  
Vol 185 (10) ◽  
pp. 6348-6354 ◽  
Author(s):  
Zhi-Jian Ye ◽  
Qiong Zhou ◽  
Yong-Yao Gu ◽  
Shou-Ming Qin ◽  
Wan-Li Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Cd4 T Cells ◽  
Malignant Pleural Effusion

Effects of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) on proliferation and cytokine secretion of immune cells in malignant pleural effusion

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3046-3046
Author(s):  
M. Sebastian ◽  
M. Jaeger ◽  
P. Kiewe ◽  
W. Schuette ◽  
R. Wiewrodt ◽  
...  
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Tumor Cells ◽  
Pleural Fluid ◽  
Immune Cells ◽  
Malignant Pleural Effusion ◽  
Cytokine Secretion ◽  
Accessory Cells ◽  
Ifn Γ

3046 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via FcγR I/III. Thus the antibody induces tumor specific cell mediated cytotoxicity in vitro and in vivo. Following last years’ ASCO presentation on a phase I/II trial showing safety and efficacy of repetitive intrapleural administration of catumaxomab in patients with EpCAM positive, malignant pleural effusion (MPE), we now present data on the responsiveness of immune cells from pleural fluid to catumaxomab. Methods: Pleural fluid of patients with EpCAM-positive MPE treated with i.pl. catumaxomab was collected before treatment. Cells were harvested from the fluid and cultured ± 100 ng/ml catumaxomab using an in vitro proliferation assay. After 72 h of culture, proliferation of T cells (CD4+ and CD8+) and monocytes (CD11c+) was determined. In addition, cell supernatants after 24h incubation ± catumaxomab were analysed for their TH1/TH2 cytokine profile (IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF- a). Results: Incubation in presence of catumaxomab led to a pronounced increase of CD4+ CD8+ and CD11+ cell numbers indicating a proliferation of these cells, whereas cultures without catumaxomab showed no proliferation of immune cells. Analysis of supernatants after 24 h revealed levels of IL-2, IL-6, IFN-γ and TNF-a, from cells incubated with catumaxomab that were distinctly higher than in cultures without catumaxomab. Conclusions: The immunologic nature of catumaxomab-induced responses in patients with pleural effusion accompanied by a reduction of tumor cells, could be underlined impressively with in vitro data obtained from pleural cells showing catumaxomab-induced proliferation of T cells and accessory cells and TH1-directed cytokine secretion. The data are equivalent to results observed in the peritoneal fluid of ascites patients. [Table: see text]

scholarly journals Single-cell analysis of diverse immune phenotypes in malignant pleural effusion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhong-Yin Huang ◽  
Ming-Ming Shao ◽  
Jian-Chu Zhang ◽  
Feng-Shuang Yi ◽  
Juan Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
B Cells ◽  
Pleural Effusion ◽  
Small Cell Lung Cancer ◽  
Single Cell ◽  
Immune Cells ◽  
Malignant Pleural Effusion ◽  
Small Cell ◽  
Small Cell Lung

AbstractThe complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer.

scholarly journals Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinying Li ◽  
Guannan Wu ◽  
Cen Chen ◽  
Yuan Zhao ◽  
Suhua Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Cd8 T Cells ◽  
Malignant Pleural Effusion ◽  
Malignant Tumors ◽  
Cytotoxic T Cells ◽  
Lymphocyte Activation ◽  
Local Injection ◽  
And Function ◽  
Nsclc Patients

BackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observed via flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.ResultsIntrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).ConclusionsIntrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.

scholarly journals IRF4 is Correlated With the Conversion to a Th17-like Phenotype in Regulatory T Cells From the Malignant Pleural Effusion

2021 ◽  
Author(s):  
Wen-qing Yu ◽  
Ningfei Ji ◽  
Chengjing Gu ◽  
Juan Yao ◽  
Mingdong Ding ◽  
...  
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Regulatory T Cells ◽  
Protein Expression ◽  
Malignant Pleural Effusion ◽  
Mononuclear Cells ◽  
Double Positive ◽  
Relative Level ◽  
Treg Subset

Abstract Background: RORγt+Foxp3+ (Th17-like) Tregs are a plastic Treg subset implicated in immune-related diseases; however, the mechanism of Treg phenotypic transformation in malignant pleural effusion (MPE) has not been elucidated.Methods: The percentage of CD4+CD25+Foxp3+Helios+ and RORγt+Foxp3+ Tregs from peripheral blood and pleural effusion mononuclear cells were measured. The level of interferon regulatory factor 4 (IRF4) mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction. The effects of IRF4 on the induction of Tregs from patients with non-small cell lung cancer (NSCLC) were evaluated in vitro. Correlation assays between IRF4 expression and the frequency of RORγt+Foxp3+ Tregs were performed. Results: The frequency of CD4+CD25+Foxp3+Helios+ Tregs and CD4+RORγt+ Th17 cells were both increased in the MPE of NSCLC patients. The group of double-positive Foxp3+RORγt+ Treg phenotype were identified in the pleural effusion. A significant increase in the frequency of Foxp3+RORγt+ Tregs was found in MPE compared with the non-malignant pleural effusion (NPE). Compared to NPE, the relative level of IRF4 expression was increased in the MPE. IRF4 expression was positively associated with the frequency of Foxp3+RORγt+ Tregs in the PE. In vitro, the level of Helios mRNA and protein expression was reduced in induced Tregs following IRF4 over-expression. Additionally, the level of RORγt protein expression was substantially increased. However, ectopic Helios expression in induced Tregs reversed the effects induced by enhanced IRF4 expression.Conclusion: IRF4 may serve as a potential molecule that promotes the conversion of regulatory T cells from MPE to a Th17-like phenotype by modulating Helios.

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