Association between effector-type regulatory T cells and immune checkpoint expression on CD8+ T cells in malignant ascites from epithelial ovarian cancer

2022 ◽  
Author(s):  
Sho Sato ◽  
Hirokazu Matsushita ◽  
Daisuke Shintani ◽  
Nao Fujieda ◽  
Akira Yabuno ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Epithelial Ovarian Cancer ◽  
Immune Checkpoint ◽  
Malignant Ascites ◽  
Serous Carcinoma ◽  
Median Frequency ◽  
Color Flow ◽  
Inhibitory Networks

Abstract Background Regulatory T cells (Tregs) play an important role in the antitumor immune response in epithelial ovarian cancer (EOC). To understand the immune-inhibitory networks of EOC, we addressed the association between Tregs and immune checkpoint expression on T cells in the tumor microenvironment of EOC Methods A total of 41 patients with stage IIIC and IV EOC were included in the analysis. We harvested cells from malignant ascites and investigated them using multi-color flow cytometry. We categorized the Tregs into 3 groups: effector-type Tregs, naïve Tregs and non-Tregs, based on the expression patterns of CD45RA and Foxp3 in CD4+ T cells. Furthermore, the relationships between the expression of various immune checkpoint molecules, such as PD-1, on CD8+T cells and each of the Treg subtypes was also evaluated. Results The median frequency of naïve Tregs, effector-type Tregs and non-Tregs were 0.2% (0-0.8), 2.0% (0-11.4) and 1.5% (0.1-6.3) in CD4+ T cells of malignant ascites from EOC patients, respectively. A high frequency of effector-type Tregs was associated with high-grade serous carcinoma compared with the other histotypes. Patients with higher proportions of effector-type Tregs showed a trend towards increased progression-free survival. We also demonstrated a correlation between a higher proportion of effector-type Tregs and increased PD-1 expression on CD8+ T cells. In addition, C-C chemokine receptor 4 expression was also observed in effector-type Tregs. Conclusion These data suggest that multiple immune-inhibitory networks exist in malignant ascites from EOC patients, suggesting an approach towards combinational immunotherapies for advanced EOC patients.

scholarly journals Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer

2015 ◽  
Vol 64 (12) ◽  
pp. 1495-1504 ◽  
Author(s):  
Keith L. Knutson ◽  
Matthew J. Maurer ◽  
Claudia C. Preston ◽  
Kirsten B. Moysich ◽  
Krista Goergen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Clinical Outcome ◽  
Epithelial Ovarian Cancer

Correlation of Wilms' tumor 1 (WT1) expression with infiltration by regulatory T cells (Tregs) in epithelial ovarian cancer

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 5578-5578
Author(s):  
N. E. Tchabo ◽  
A. F. Beck ◽  
A. J. Miliotto ◽  
E. Sato ◽  
C. Andrews ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Epithelial Ovarian Cancer ◽  
Wilms Tumor ◽  
Wilms Tumor 1

scholarly journals Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma

2021 ◽  
Vol 14 (9) ◽  
pp. 101170
Author(s):  
Vera Bauer ◽  
Fatima Ahmetlić ◽  
Nadine Hömberg ◽  
Albert Geishauser ◽  
Martin Röcken ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Immune Checkpoint ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

scholarly journals O4 Mechanisms of lung cancer hyper-progression promoted by PD-1 immune checkpoint blockade

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A5.1-A5
Author(s):  
A Martinez-Usatorre ◽  
E Kadioglu ◽  
C Cianciaruso ◽  
B Torchia ◽  
J Faget ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Genetically Engineered ◽  
Checkpoint Blockade ◽  
Therapeutic Benefits ◽  
Angiopoietin 2

BackgroundImmune checkpoint blockade (ICB) with antibodies against PD-1 or PD-L1 may provide therapeutic benefits in patients with non-small cell lung cancer (NSCLC). However, most tumours are resistant and cases of disease hyper-progression have also been reported.Materials and MethodsGenetically engineered mouse models of KrasG12Dp53null NSCLC were treated with cisplatin along with antibodies against angiopoietin-2/VEGFA, PD-1 and CSF1R. Tumour growth was monitored by micro-computed tomography and the tumour vasculature and immune cell infiltrates were assessed by immunofluorescence staining and flow cytometry.ResultsCombined angiopoietin-2/VEGFA blockade by a bispecific antibody (A2V) modulated the vasculature and abated immunosuppressive macrophages while increasing CD8+effector T cells in the tumours, achieving disease stabilization comparable or superior to cisplatin-based chemotherapy. However, these immunological responses were unexpectedly limited by the addition of a PD-1 antibody, which paradoxically enhanced progression of a fraction of the tumours through a mechanism involving regulatory T cells and macrophages. Elimination of tumour-associated macrophages with a CSF1R-blocking antibody induced NSCLC regression in combination with PD-1 blockade and cisplatin.ConclusionsThe immune cell composition of the tumour determines the outcome of PD-1 blockade. In NSCLC, high infiltration of regulatory T cells and immunosuppressive macrophages may account for tumour hyper-progression upon ICB.Disclosure InformationA. Martinez-Usatorre: None. E. Kadioglu: None. C. Cianciaruso: None. B. Torchia: None. J. Faget: None. E. Meylan: None. M. Schmittnaegel: None. I. Keklikoglou: None. M. De Palma: None.

scholarly journals Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives

Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 146 ◽  
Author(s):  
Fulvio Borella ◽  
Eleonora Ghisoni ◽  
Gaia Giannone ◽  
Stefano Cosma ◽  
Chiara Benedetto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Approaches ◽  
Medical Treatments ◽  
New Therapeutic Approaches ◽  
Early Phase Trials ◽  
Improve Patient

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of several cancers and are under evaluation in OC. Unfortunately, CPIs have shown globally unsatisfactory results. The aim of this manuscript is to critically review the results from early-phase trials with CPIs in terms of safety and activity, discuss the possible reasons for disappointing results and the new therapeutic approaches to improve patient outcomes.

Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma

2018 ◽  
Vol 24 (22) ◽  
pp. 5685-5696 ◽  
Author(s):  
Aras Toker ◽  
Linh T. Nguyen ◽  
Simone C. Stone ◽  
S.Y. Cindy Yang ◽  
Sarah Rachel Katz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Regulatory T Cells
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