Vick, Logan VV, Collins, Craig PP, Khuat, Lam TT, Wang, Ziming, Dunai, Cordelia 
ORCID: 0000-0001-5799-2387, Aguilar, Ethan GG, Stoffel, Kevin, Yendamuri, Sai, Smith Jr, Randall, Mukherjee, Sarbajit et al (show 4 more authors)
(2023)
Aging augments obesity-induced thymic involution and peripheral T cell exhaustion altering the "obesity paradox".
FRONTIERS IN IMMUNOLOGY, 13.
1012016-.
|
PDF
Aging augments obesity-induced thymic involution and peripheral T cell exhaustion altering the obesity paradox.pdf - Open Access published version Download (6MB) | Preview |
Abstract
<h4>Introduction</h4>The incidence of obesity, a condition characterized by systemic chronic inflammation, has reached pandemic proportions and is a poor prognostic factor in many pathologic states. However, its role on immune parameters has been diverse and at times contradictory. We have previously demonstrated that obesity can result in what has been called the "obesity paradox" which results in increased T cell exhaustion, but also greater efficacy of immune checkpoint blockade in cancer treatment.<h4>Methods</h4>The role of obesity, particularly in the context of aging, has not been robustly explored using preclinical models. We therefore evaluated how age impacts the immune environment on T cell development and function using diet-induced obese (DIO) mice.<h4>Results</h4>We observed that DIO mice initially displayed greater thymopoiesis but then developed greater thymic involution over time compared to their lean counterparts. Both aging and obesity resulted in increased T cell memory conversion combined with increased expression of T cell exhaustion markers and Treg expansion. This increased T cell immunosuppression with age then resulted in a loss of anti-tumor efficacy by immune checkpoint inhibitors (ICIs) in older DIO mice compared to the younger DIO counterparts.<h4>Discussion</h4>These results suggest that both aging and obesity contribute to T cell dysfunction resulting in increased thymic involution. This combined with increased T cell exhaustion and immunosuppressive parameters affects immunotherapy efficacy reducing the advantage of obesity in cancer immunotherapy responses.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | obesity, T cell, immunotherapy, inflammaging, aging, thymic involution, PD-1 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 19 Apr 2023 10:13 |
| Last Modified: | 19 Apr 2023 10:13 |
| DOI: | 10.3389/fimmu.2022.1012016 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169745 |
Dimensions
Dimensions
