Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.
EMBO Rep
; 25(8): 3601-3626, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38956225
ABSTRACT
Signals emanating from the T-cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T-cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T-cell function. Through forward genetic screening in mice, we discover that loss-of-function mutations in LDL receptor-related protein 10 (Lrp10) cause naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. T-cell activation induces Lrp10 expression, which post-translationally suppresses IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhances T-cell homeostatic expansion through IL7R signaling. Lrp10-deficient mice are also intrinsically resistant to syngeneic tumors. This phenotype depends on dense tumor infiltration of CD8 T cells, which display increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T-cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD8-Positive T-Lymphocytes
/
Receptors, Interleukin-7
/
Homeostasis
Limits:
Animals
/
Humans
Language:
En
Journal:
EMBO Rep
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos