Abstract P4-03-08: Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer

Author(s):  
T Gruosso ◽  
M Gigoux ◽  
N Bertos ◽  
D Zuo ◽  
V Manem ◽  
...  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Katherine J. Carpenter ◽  
Aurore-Cecile Valfort ◽  
Nick Steinauer ◽  
Arindam Chatterjee ◽  
Suomia Abuirqeba ◽  
...  

AbstractTriple-negative breast cancer (TNBC) is a highly aggressive subtype that is untreatable with hormonal or HER2-targeted therapies and is also typically unresponsive to checkpoint-blockade immunotherapy. Within the tumor microenvironment dysregulated immune cell metabolism has emerged as a key mechanism of tumor immune-evasion. We have discovered that the Liver-X-Receptors (LXRα and LXRβ), nuclear receptors known to regulate lipid metabolism and tumor-immune interaction, are highly activated in TNBC tumor associated myeloid cells. We therefore theorized that inhibiting LXR would induce immune-mediated TNBC-tumor clearance. Here we show that pharmacological inhibition of LXR activity induces tumor destruction primarily through stimulation of CD8+ T-cell cytotoxic activity and mitochondrial metabolism. Our results imply that LXR inverse agonists may be a promising new class of TNBC immunotherapies.


2016 ◽  
Author(s):  
Tina Gruosso ◽  
Mathieu Gigoux ◽  
Nicholas Bertos ◽  
Sadiq Saleh ◽  
Atilla Omeroglu ◽  
...  

2020 ◽  
Vol 21 (18) ◽  
pp. 6968 ◽  
Author(s):  
Masanori Oshi ◽  
Mariko Asaoka ◽  
Yoshihisa Tokumaru ◽  
Li Yan ◽  
Ryusei Matsuyama ◽  
...  

CD8 T cell is an essential component of tumor-infiltrating lymphocytes (TIL) and tumor immune microenvironment (TIME). Using the xCell CD8 T cell score of whole tumor gene expression data, we estimated these cells in total of 3837 breast cancer patients from TCGA, METABRIC and various GEO cohorts. The CD8 score correlated strongly with expression of CD8 genes. The score was highest for triple-negative breast cancer (TNBC), and a high score was associated with high tumor immune cytolytic activity and better survival in TNBC but not other breast cancer subtypes. In TNBC, tumors with a high CD8 score had enriched expression of interferon (IFN)-α and IFN-γ response and allograft rejection gene sets, and greater infiltration of anti-cancerous immune cells. The score strongly correlated with CD4 memory T cells in TNBC, and tumors with both a high CD8 score and high CD4 memory T cell abundance had significantly better survival. Finally, a high CD8 score was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, a high CD8 T cell score is associated with better survival in TNBC, particularly when tumor CD4 memory T cells were elevated. Our findings also suggest a possible use of the score as a predictive biomarker for response to immune checkpoint therapy.


2019 ◽  
Vol 9 (6) ◽  
pp. 722-737 ◽  
Author(s):  
Constantia Pantelidou ◽  
Olmo Sonzogni ◽  
Mateus De Oliveria Taveira ◽  
Anita K. Mehta ◽  
Aditi Kothari ◽  
...  

2016 ◽  
Author(s):  
Lisa I. Greene ◽  
Tullia C. Bruno ◽  
Thomas J. Rogers ◽  
Jill E. Slansky ◽  
Virginia F. Borges ◽  
...  

2021 ◽  
Vol 85 ◽  
pp. 104664
Author(s):  
Mohan Li ◽  
Kexin Zheng ◽  
Shiliang Ma ◽  
Pengpeng Hu ◽  
Bo Yuan ◽  
...  

2021 ◽  
Vol 360 ◽  
pp. 104262
Author(s):  
Pengxiang Yang ◽  
Xingjian Cao ◽  
Huilong Cai ◽  
Panfeng Feng ◽  
Xiang Chen ◽  
...  

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