| RRC ID |
78420
|
| 著者 |
Srirat T, Hayakawa T, Mise-Omata S, Nakagawara K, Ando M, Shichino S, Ito M, Yoshimura A.
|
| タイトル |
NR4a1/2 deletion promotes accumulation of TCF1+ stem-like precursors of exhausted CD8+ T cells in the tumor microenvironment.
|
| ジャーナル |
Cell Rep
|
| Abstract |
T cell exhaustion impairs tumor immunity and contributes to resistance against immune checkpoint inhibitors. The nuclear receptor subfamily 4 group A (NR4a) family of nuclear receptors plays a crucial role in driving T cell exhaustion. In this study, we observe that NR4a1 and NR4a2 deficiency in CD8+ tumor-infiltrating lymphocytes (TILs) results in potent tumor eradication and exhibits not only reduced exhaustion characteristics but also an increase in the precursors/progenitors of exhausted T (Pre-Tex) cell fraction. Serial transfers of NR4a1-/-NR4a2-/-CD8+ TILs into tumor-bearing mice result in the expansion of TCF1+ (Tcf7+) stem-like Pre-Tex cells, whereas wild-type TILs are depleted upon secondary transfer. NR4a1/2-deficient CD8+ T cells express higher levels of stemness/memory-related genes and illustrate potent mitochondrial oxidative phosphorylation. Collectively, these findings suggest that inhibiting NR4a in tumors represents a potent immuno-oncotherapy strategy by increasing stem-like Pre-Tex cells and reducing exhaustion of CD8+ T cells.
|
| 巻・号 |
43(3)
|
| ページ |
113898
|
| 公開日 |
2024-3-5
|
| DOI |
10.1016/j.celrep.2024.113898
|
| PII |
S2211-1247(24)00226-2
|
| PMID |
38451819
|
| リソース情報 |
| ヒト・動物細胞 |
B16 melanoma(RCB1283) |
| 実験動物マウス |
RBRC00144 |
