Defect in recruiting effector memory CD8+T-cells in malignant pleural effusions compared to normal pleural fluid

Scherpereel, Arnaud; Grigoriu, Bogdan; Noppen, Marc; Gey, Thomas; Chahine, Bachar; Baldacci, S.; Trauet, Jacques; Copin, Marie‐Christine; Dessaint, Jean-Paul; Porte, Henri; Labalette, Myriam

doi:10.1186/1471-2407-13-324

Cited by 40 publications

(40 citation statements)

References 51 publications

(54 reference statements)

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“…Cytokines that possess immune-inhibitory properties and are abundant in the malignancy-affected pleural cavity, as well as local accumulation of immunosuppressive and protumour CD4 + lymphocytes, contribute to immune evasion and facilitate tumour growth [17][18][19][20][21]. Relative to this, MPE is characterised by defective recruitment, activation and the cytotoxic potential of CD8 + cells [22,23]. Macrophages from malignant effusions not only display reduced cytotoxic activity against autologous tumour cells but they also inhibit tumour cell apoptosis [24,25].…”

Section: Pathophysiology Of Mpementioning

confidence: 99%

Malignant pleural effusion: from bench to bedside

et al. 2016

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Malignant pleural effusion (MPE) is a common but serious condition that is related with poor quality of life, morbidity and mortality. Its incidence and associated healthcare costs are rising and its management remains palliative, with median survival ranging from 3 to 12 months. During the last decade there has been significant progress in unravelling the pathophysiology of MPE, as well as its diagnostics, imaging, and management. Nowadays, formerly bed-ridden patients are genotyped, phenotyped, and treated on an ambulatory basis. This article attempts to provide a comprehensive overview of current advances in MPE from bench to bedside. In addition, it highlights unanswered questions in current clinical practice and suggests future directions for basic and clinical research in the field. @ERSpublications This review provides up to date knowledge for malignant pleural effusion covering aspects from bench to bedside http://ow.ly/10w7vN

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Section: Pathophysiology Of Mpementioning

confidence: 99%

Malignant pleural effusion: from bench to bedside

et al. 2016

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“…In our previous study, we found that the expressions of six miRNAs were increased in the longer survival group of patients with NSCLC, namely miR134, miR141, miR106b, miR224, miR720, and miR1260 (8). We then applied the prediction programs TargetScan and miRanda to identify the potential regulators of CXCL1, and found that CXCL1 has putative miR141-binding elements in the 3 0 UTRs (Fig.…”

Section: Mir141 Regulates Expression Of Cxcl1 In Lung Cancersmentioning

confidence: 99%

“…The proportion of Tregs increased in an advanced stage of NSCLC (7). Moreover, pleural fluid from benign disease contained mainly CD8 þ T cells, whereas MPEs included mainly CD4 þ T cells (8). Therefore, it is reasonable to assume that Tregs could be upregulated by tumor cells in MPE and eventually affect patient survival.…”

Section: Introductionmentioning

confidence: 99%

miR141–CXCL1–CXCR2 Signaling–Induced Treg Recruitment Regulates Metastases and Survival of Non–Small Cell Lung Cancer

Tang

et al. 2014

Molecular Cancer Therapeutics

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Patients with non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE) have a short median survival time and increased regulatory T cells (Treg). However, it is unclear whether some specific factors in MPE are involved in Treg recruitment in the progression of NSCLC. Here, we found that Treg population was increased in MPE and inversely correlated with patient survival (P < 0.001). Increased level of CXCL1 in MPE was associated with recruitment of Tregs (P < 0.01). Moreover, miR141 regulated expression of CXCL1 in lung cancer cells, whereas the luciferase test confirmed that CXCL1 is a target of miR141. Chemotaxis assay showed that the miR141-CXCL1-CXCR2 pathway regulates migration of Tregs into MPE. Furthermore, miR141 significantly inhibited tumor growth and metastasis in an immunecompetent mouse model. This suppressive function was mediated by the CXCL1-CXCR2 pathway and recruitment of Tregs. Our study uncovered a causative link between microRNA and development of MPE. Mechanistically, decreased expressions of miR141, associated with the survival of patients with NSCLC with MPE, resulted in the increased production of CXCL1 and recruitment of Tregs to promote immune escape of tumor. Mol Cancer Ther; 13(12); 3152-62. Ó2014 AACR.

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“…This inflammatory process may be provoked by the cancer or by other nonmalignant diseases and causes the accumulation of fluid in the pleural space . Malignant pleural effusions are frequently infiltrated by tumour and immune cells, but the T cells that infiltrate the pleura are dysfunctional, as evidenced by their low proliferation rate, cytokine production and cytolytic activity . Remarkably, the T cell dysfunction found in T cells from pleural effusions is similar to that observed in tumour‐infiltrating lymphocytes (TILs) in lung cancer, suggesting that the tumour evasion mechanisms in the two environments are similar .…”

Section: Introductionmentioning

confidence: 94%

Deficient glucose uptake is linked to impaired Glut1 expression upon CD3/CD28 stimulation in memory T cells from pleural effusions secondary to lung cancer

et al. 2019

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Glucose and nutrient uptake is essential in supporting T cell activation and is increased upon CD3/CD28 stimulation. As T cells from pleural effusions secondary to lung cancer show impaired function, we hypothesized that these cells might have altered expression of nutrient transporters. Here, we analysed by flow cytometry the expression of the transferrin receptor CD71, amino acid transporter CD98 and glucose transporter Glut1 and glucose uptake in pleural effusion‐derived T cells from lung cancer patients, after stimulation via CD3/CD28 under normoxia or hypoxia (2% O2). We compared the response of T cells from pleural effusions secondary to lung cancer with that of T cells from nonmalignant effusions. In memory T cells from both groups, anti‐CD3/CD28‐stimulation under normoxia upregulated CD98 and CD71 expression (measured as median fluorescence intensity, MFI) in comparison with anti‐CD3‐stimulation. Costimulation under hypoxia tended to increase CD98 expression compared to CD3‐stimulation in memory T cells from both groups. Remarkably, in the cancer group, memory T cells stimulated via CD3/CD28 under hypoxia failed to increase CD71 and Glut1 expression levels compared to the cells receiving anti‐CD3 stimulation, a phenomenon that contrasted with the behaviour of memory T cells from nonmalignant effusions. Consequently, glucose uptake by memory T cells from the cancer group was not increased after CD3/CD28 stimulation under hypoxia, implying that their glycolytic metabolism is defective. As this process is required for inducing an antitumoural response, our study suggests that memory T cells are rendered dysfunctional and are unable to eliminate lung tumour cells.

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Defect in recruiting effector memory CD8+T-cells in malignant pleural effusions compared to normal pleural fluid

Cited by 40 publications

References 51 publications

Malignant pleural effusion: from bench to bedside

Malignant pleural effusion: from bench to bedside

miR141–CXCL1–CXCR2 Signaling–Induced Treg Recruitment Regulates Metastases and Survival of Non–Small Cell Lung Cancer

Deficient glucose uptake is linked to impaired Glut1 expression upon CD3/CD28 stimulation in memory T cells from pleural effusions secondary to lung cancer

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