The functional role of KLRG1⁺ Tregs in Non-small Cell Lung Cancer.

Oluwaseyi E. Oluwatola*, Arup Bag, Saheed Oseni, Shari-Pilon-Thomas, Dennis Adeegbe.

*Presenter

 

---

Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B121
Abstract ID: 4127

Presenting Author:
Oluwaseyi E. Oluwatola , Graduate Student at Univ. of South Florida, Moffitt Cancer Ctr.

Abstract:

Killer cell lectin-like receptor G1 (KLRG1) is a co-inhibitory receptor and upon engagement with its ligand, E-, N-, or R-cadherins, Akt phosphorylation is inhibited leading to proliferative dysfunction in T and NK cells. This study aims to investigate how E-cadherin engagement affects KLRG1 function. 

KLRG1 fl/fl and cKO mice were orthotopically implanted with KP tumor cell line. T cells were isolated and stimulated for intracellular staining. KLRG1+ and KLRG1- Tregs sorted from lung suspensions of KPM tumors were stimulated with α-CD3+α-CD28 in the presence or absence of soluble E-cadherin for 24hours. CD4+CD25- effector T cells were labelled with cell-trace violet (CTV) and then co- cultured with graded numbers of each population of Tregs in the presence/absence of soluble E-cadherin. Finally, KLRG1+ and KLRG1- Tregs were sorted from lung tumors of KP mice for single-cell RNA sequencing.  

We show that GZB is upregulated in KLRG1+ Tregs upon engagement with E-cadherin as confirmed by RNA sequencing, and this GZB expression by KLRG1+ Tregs is associated with enhanced death of effector T cells. Also,Treg-specific deletion of KLRG1 in the cKO mice does not impact Treg development or peripheral homeostasis; instead it permits enhanced anti-tumor responses in lung adenocarcinoma-bearing mice. 

NSCLC-associated KLRG1+ Tregs are armed with a functional program that drives their enhanced immunosuppressive activity and attenuates effector function compared to KLRG1- Tregs.