Asset Details
Do you wish to reserve the book?
Optical Control of CD8+ T Cell Metabolism and Effector Functions
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Optical Control of CD8+ T Cell Metabolism and Effector Functions
Do you wish to request the book?
Optical Control of CD8+ T Cell Metabolism and Effector Functions
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Optical Control of CD8+ T Cell Metabolism and Effector Functions
2021
Overview
Although cancer immunotherapy is effective against hematological malignancies, it is less effective against solid tumors due in part to significant metabolic challenges present in the tumor microenvironment (TME), where infiltrated CD8 + T cells face fierce competition with cancer cells for limited nutrients. Strong metabolic suppression in the TME is often associated with impaired T cell recruitment to the tumor site and hyporesponsive effector function via T cell exhaustion. Increasing evidence suggests that mitochondria play a key role in CD8 + T cell activation, effector function, and persistence in tumors. In this study, we showed that there was an increase in overall mitochondrial function, including mitochondrial mass and membrane potential, during both mouse and human CD8 + T cell activation. CD8 + T cell mitochondrial membrane potential was closely correlated with granzyme B and IFN-γ production, demonstrating the significance of mitochondria in effector T cell function. Additionally, activated CD8 + T cells that migrate on ICAM-1 and CXCL12 consumed significantly more oxygen than stationary CD8 + T cells. Inhibition of mitochondrial respiration decreased the velocity of CD8 + T cell migration, indicating the importance of mitochondrial metabolism in CD8 + T cell migration. Remote optical stimulation of CD8 + T cells that express our newly developed “OptoMito-On” successfully enhanced mitochondrial ATP production and improved overall CD8 + T cell migration and effector function. Our study provides new insight into the effect of the mitochondrial membrane potential on CD8 + T cell effector function and demonstrates the development of a novel optogenetic technique to remotely control T cell metabolism and effector function at the target tumor site with outstanding specificity and temporospatial resolution.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
Adenosine Triphosphate - metabolism
/ Animals
/ Antigens
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ CD8-Positive T-Lymphocytes - radiation effects
/ Cell Movement - radiation effects
/ Cytoskeleton - radiation effects
/ Humans
/ Hypoxia
/ Intercellular adhesion molecule 1
/ Lymphocyte Activation - radiation effects
/ Membrane Potential, Mitochondrial - genetics
/ Membrane Potential, Mitochondrial - radiation effects
/ Mice
/ Mitochondria - radiation effects
/ Tumors
