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
3157 - Efficacy and safety of anlotinib in advanced leiomyosarcoma: Subgroup analysis of a phase IIB trial (ALTER0203)
Presenter: Yihebali Chi
Session: Poster Display session 1
Resources:
Abstract
3710 - The effect of treatment line on the efficacy of Anlotinib hydrochloride in advanced alveolar soft part sarcoma patients
Presenter: Zhiwei Fang
Session: Poster Display session 1
Resources:
Abstract
3184 - Prior exposure to pazopanib (PAZ) did not minor efficacy of regorafenib (REG) in non-adipocytic soft tissue sarcoma patients (pts)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
798 - Pexidartinib (Pex) for locally advanced tenosynovial giant cell tumor (TGCT): characterization of hepatic adverse reactions (ARs)
Presenter: Sebastian Bauer
Session: Poster Display session 1
Resources:
Abstract
6117 - VEGFR2 and ITGA polymorphisms as novel pan-sarcoma biomarkers for sensitivity prediction as well as toxicity prevention anti-angiogenesis therapy in pediatric and young adult
Presenter: Qiyuan Bao
Session: Poster Display session 1
Resources:
Abstract
5450 - Reversion of resistance to mTOR inhibitors with the addition of exemestane in patients with malignant PEComa.
Presenter: Roberta Sanfilippo
Session: Poster Display session 1
Resources:
Abstract
4279 - Efficacy and Safety of VEGFR2 Inhibitor Apatinib combined with chemotherapy for Sarcoma in Stage IV
Presenter: Zhiwu Ren
Session: Poster Display session 1
Resources:
Abstract
5929 - Outcomes of metastatic soft tissue sarcoma treated with Pazopanib from dedicated medical oncology sarcoma clinic: A holistic care approach from a developing country
Presenter: Akhil Kapoor
Session: Poster Display session 1
Resources:
Abstract
2469 - Inhibition of mTOR signaling enhances Trabectedin activity in Soft Tissue Sarcoma
Presenter: David Moura
Session: Poster Display session 1
Resources:
Abstract
4210 - Efficacy and safety of apatinib for advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib: An open-label, multicenter, single-arm, phase II trial
Presenter: Zhaolun Cai
Session: Poster Display session 1
Resources:
Abstract