Abstract 5400
Background
Type 1 regulatory (Tr1) T cells, like every effector T cells, arise from stimulation of naïve T cell precursor and enter a long term memory pool. While they can adapt their function to specific environmental cues, sometimes called plasticity, their phenotype remains broadly fixed. Unlike natural T regulator cells that emerge from the thymus with a defined phenotype (CD4+CD25hiCD127loFoxP3+), there is uncertainty over the characterisation of inducible Tr1 cells.
Methods
In this study we stimulated human total CD4+ T cells with PMA/ Ionomycin and also demonstrated that these cells respond specifically to costimulation via CD97-CD55. Dual cell surface capture (CSA) was used to assay for IL-10 and IFN-γ and intracellular staining for Tr1 markers.
Results
A small (<5%) population were IL-10+ IL-4-, IFN-γ- and expressed other markers commonly associated with Tr1-like cells. These included; CD49b, LAG-3, CD226, PD-1, CTLA-4, and TIM-3. However they were negative for FoxP3 expression, and expressed Cmaf, which is thought to be responsible for the transcriptional events within this population. Furthermore, we show that these Tr1-like cells form part of the immunological memory and reside predominantly within the effector memory (CD62L- CD45RO+, TEM) pool. Unlike the majority of other studies where Tr1 is generated by chronic stimulation of PBMCs in the presence of recombinant IL-10 for several days, as far as we are aware, this is the first report characterising Tr1 directly ex vivo from human peripheral blood.
Conclusions
We have also demonstrated that these cells respond specifically to costimulation via CD97-CD55 to drive proliferation and maintain the IL-10 single positive, Tr1 phenotype outlined above. This supports the idea that once differentiated from naïve precursors, Tr1-like cells respond to CD55 costimulation to maintain a small (<5%) pool with a committed IL-10+ IL-4-IFN-γ- phenotype.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The University of Nottingham.
Funding
The Commonwealth Scholarships Commission, London.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract
4325 - Multiple synchronous mechanisms may contribute to osimertinib resistance in non-small cell lung cancer (NSCLC) patients: insights of the MATCH-R study
Presenter: Diego Enrico
Session: Poster Display session 1
Resources:
Abstract