scholarly journals Cholesterol-lowering Decreased mTOR Complex 2 Signaling and Enhanced Antitumor Immunity

2021 ◽  
Author(s):  
Yanping Wang ◽  
Sungyong You ◽  
Shengchen Su ◽  
Austin Yeon ◽  
Eric M. Lo ◽  
...  
Keyword(s):  
T Cell ◽  
Serum Cholesterol ◽  
Antitumor Immunity ◽  
Cd8 T Cell ◽  
T Cell Memory ◽  
Lymphocyte Function ◽  
Dependent Manner ◽  
Cell Memory ◽  
Cholesterol Lowering ◽  
Cd8 T Cell Memory

SummaryCholesterol-lowering interventions are employed widely and safely to reduce risk of cardiovascular disease. Cholesterol may have complex and opposing effects on immunity. We lowered serum cholesterol to clinically relevant levels in mice and evaluated the final adaptive immune response. Mice treated with oral ezetimibe exhibited enhanced antitumor immunity against syngeneic cancers in a CD8+ lymphocyte-dependent manner, produced immunity that was transferrable through lymphocytes, and enhanced central CD8+ T cell memory. In both mice and patients undergoing prostatectomy, lowering serum cholesterol inhibited mTORC2 signaling in lymphocytes and increased infiltration of CD8+ lymphocytes into prostate tumors. Lymphocyte-specific mTORC2 knockout mice demonstrated enhanced CD8+ lymphocyte function and antitumor capacity. In a prospective clinical trial, cholesterol-lowering intervention prior to prostatectomy decreased the proliferation of normal prostate and low-grade adenocarcinomas. Here, we show that lowering serum cholesterol may be an effective strategy to decrease signaling through mTORC2 and enhance antitumor CD8+ T cell memory.

scholarly journals Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner

Cell Reports ◽  
2016 ◽  
Vol 14 (5) ◽  
pp. 1206-1217 ◽  
Author(s):  
Lianjun Zhang ◽  
Benjamin O. Tschumi ◽  
Isabel C. Lopez-Mejia ◽  
Susanne G. Oberle ◽  
Marten Meyer ◽  
...  
Keyword(s):  
T Cell ◽  
Mammalian Target Of Rapamycin ◽  
Cd8 T Cell ◽  
Target Of Rapamycin ◽  
T Cell Memory ◽  
Dependent Manner ◽  
Cell Memory ◽  
Memory Differentiation ◽  
Cd8 T Cell Memory

scholarly journals Autophagy is a critical regulator of memory CD8+ T cell formation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Daniel J Puleston ◽  
Hanlin Zhang ◽  
Timothy J Powell ◽  
Elina Lipina ◽  
Stuart Sims ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Bulk Material ◽  
Cd8 T Cell ◽  
Memory Formation ◽  
T Cell Memory ◽  
Dependent Manner ◽  
Cell Memory ◽  
Cd8 T Cell Memory

During infection, CD8+ T cells initially expand then contract, leaving a small memory pool providing long lasting immunity. While it has been described that CD8+ T cell memory formation becomes defective in old age, the cellular mechanism is largely unknown. Autophagy is a major cellular lysosomal degradation pathway of bulk material, and levels are known to fall with age. In this study, we describe a novel role for autophagy in CD8+ T cell memory formation. Mice lacking the autophagy gene Atg7 in T cells failed to establish CD8+ T cell memory to influenza and MCMV infection. Interestingly, autophagy levels were diminished in CD8+ T cells from aged mice. We could rejuvenate CD8+ T cell responses in elderly mice in an autophagy dependent manner using the compound spermidine. This study reveals a cell intrinsic explanation for poor CD8+ T cell memory in the elderly and potentially offers novel immune modulators to improve aged immunity.

CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death

Nature ◽  
2005 ◽  
Vol 434 (7029) ◽  
pp. 88-93 ◽  
Author(s):  
Edith M. Janssen ◽  
Nathalie M. Droin ◽  
Edward E. Lemmens ◽  
Michael J. Pinkoski ◽  
Steven J. Bensinger ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Activation Induced Cell Death ◽  
Cd4 T Cell Help ◽  
Cd8 T Cell Memory ◽  
T Cell Help

scholarly journals Apoptosis and loss of virus-specific CD8+ T-cell memory

2004 ◽  
Vol 16 (3) ◽  
pp. 271-276 ◽  
Author(s):  
Raymond M Welsh ◽  
Kapil Bahl ◽  
Xiaoting Z Wang
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cd8 T Cell Memory

Beneficial and Detrimental Manifestations of Age on CD8+ T-Cell Memory to Respiratory Pathogens

2009 ◽  
pp. 979-995
Author(s):  
Jacob E. Kohlmeier ◽  
Kenneth H. Ely ◽  
Alan D. Roberts ◽  
Eric J. Yager ◽  
Marcia A. Blackman ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Memory ◽  
Respiratory Pathogens ◽  
Cell Memory ◽  
Cd8 T Cell Memory
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