scholarly journals 032 Bach2 suppresses tumor immunity by repressing effector function-related gene in CD8 + T cells

2017 ◽  
Vol 137 (5) ◽  
pp. S6
Author(s):  
Y. Sato ◽  
M. Matsui-Watanabe ◽  
D.R. Sharda ◽  
K. Igarashi ◽  
R. Okuyama
2017 ◽  
Vol 137 (10) ◽  
pp. S249
Author(s):  
Y. Sato ◽  
M. Matsui-Watanabe ◽  
M. Matsumoto ◽  
D.R. Sharda ◽  
K. Igarashi ◽  
...  

2017 ◽  
Vol 86 (2) ◽  
pp. e66
Author(s):  
Yuki Sato ◽  
Miki Watanabe-Matsui ◽  
Daniel R. Sharda ◽  
Kazuhiko Igarashi ◽  
Ryuhei Okuyama

2001 ◽  
Vol 167 (3) ◽  
pp. 1313-1324 ◽  
Author(s):  
Jennifer L. Cannons ◽  
Peggy Lau ◽  
Birinder Ghumman ◽  
Mark A. DeBenedette ◽  
Hideo Yagita ◽  
...  

PLoS ONE ◽  
2010 ◽  
Vol 5 (10) ◽  
pp. e13109 ◽  
Author(s):  
Yoshinori Sato ◽  
Hiroshi Takata ◽  
Naoki Kobayashi ◽  
Sayaka Nagata ◽  
Naomi Nakagata ◽  
...  

2000 ◽  
Vol 164 (3) ◽  
pp. 1148-1152 ◽  
Author(s):  
Mikaël J. Pittet ◽  
Daniel E. Speiser ◽  
Danila Valmori ◽  
Jean-Charles Cerottini ◽  
Pedro Romero

Author(s):  
Qiang Shan ◽  
Sheng’en Hu ◽  
Xia Chen ◽  
Derek B. Danahy ◽  
Vladimir P. Badovinac ◽  
...  
Keyword(s):  
T Cells ◽  

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A570-A570
Author(s):  
Chen Zhao ◽  
Matthew Mule ◽  
Andrew Martins ◽  
Iago Pinal Fernandez ◽  
Renee Donahue ◽  
...  

BackgroundImmune checkpoint inhibitors (ICIs) have changed the cancer treatment landscape, but immune-related adverse events (irAEs) can affect a wide range of tissues in patients receiving ICIs. Severe irAEs can be life-threatening or fatal and prohibit patients from receiving further ICI treatment. While the clinical features of irAEs are well documented, the pathological mechanisms and predictive biomarkers are largely unknown. In addition, there is a critical need to preserve ICI-induced anti-tumor immunity while controlling for irAEs, which requires deciphering molecular and cellular signatures associated specifically with irAEs beyond those more generally linked to anti-tumor immunity.MethodsTo unbiasedly identify immune cells and states associated with irAEs, we applied CITE-seq to measure transcripts and surface proteins (83 protein markers) from PBMCs collected from patients with thymic epithelial tumors before and after treatment with an anti-PD-L1 antibody (avelumab, NCT01772004, NCT03076554).ResultsSamples from 9 patients were analyzed. No patient had a history of pre-existing paraneoplastic autoimmune disease. Anti-tumor activity was observed in all cases, and 5 patients had clinical and/or biochemical evidence of immune-related muscle inflammation (myositis with or without myocarditis). Multilevel models applied within highly resolved cell clusters revealed transcriptional states associated with ICI response and more uniquely with irAEs. A total of 190,000 cells were included in the analysis after quality control. Most notably, CD45RA+ effector memory CD8 T cells with an mTOR transcriptional signature were highly enriched at baseline and post treatment in patients with irAEs.ConclusionsOur findings suggest the potential therapeutic avenues by using mTOR inhibitors to dampen autoimmune responses while potentially sparing anti-tumor activity, to prevent treatment discontinuation and improve clinical outcomes for cancer patients treated with ICIs.AcknowledgementsThis research was supported in part by the Intramural Research Program of the NCI (the Center for Cancer Research), NIAID and NIAMS, and through a Cooperative Research and Development Agreement between the National Cancer Institute and EMD Serono.Trial RegistrationNCT01772004, NCT03076554Ethics ApprovalThis study is approved by NCI institutional review board.


2016 ◽  
Vol 01 (01) ◽  

Backgrounds: Many studies show an immune imbalance in the tumor environment; some reports show that the T helper 1 (Th1)/ T helper 2 (Th2) ratio, the number of regulatory T-cells (Treg cells) or CD8+T-cells, and the CD8+Tcell/Treg cell ratio are associated with tumor suppression and expansion. Additionally, chemotherapy was reported to affect the immunity of patients with malignancy. Patients and Methods: Using flow cytometry we measured peripheral blood lymphocytes including non T-cells, as well as T-cell subsets such as CD3+T-cells, CD4+T-cells, CD8+T-cells, Treg cells, Th1 cells and Th2 cells before treatment, at the fourth cycle, and at 1, 3, 6 and 12 months after treatment in 21 patients with B-cell lymphoma receiving R-CHOP therapy. We also analyzed the changes in three immune indexes that reflect anti-tumor immunity (the CD4/CD8 ratio, the CD8/Treg ratio and the Th1/Th2 ratio). Results: Compared to pre-treatment there were significant decreases in the CD4/CD8 ratio between 1 month and 12 months after treatment (p<0.001, for all time points). The CD8/Treg ratio gradually increased with treatment with significant increases observed at 6 months (p=0.009) and 12 months after treatment (p=0.002). The Th1/ Th2 ratio showed a significant increase only before 4 cycles of therapy (p=0.007). Conclusion: Based on the changes in these three immune indexes, we propose that anti-tumor immunity improved after R-CHOP therapy, which enhanced the efficacy of R-CHOP therapy for lymphoma as well as its direct cytotoxic activity


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