PD-L1 – PD-1 interactions limit effector Treg cell populations at homeostasis and during infection
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ABSTRACT:
PROVIDER: PRJNA773432 | ENA |
REPOSITORIES: ENA
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Project description:While much is known about the factors that promote diverse Treg cell responses, less is known about mechanisms that constrain Treg cells. Here we demonstrate phenotypic and transcriptional profiling at homeostasis, which reveals TCR activation promotes a population of Treg cells that display an effector phenotype (eTreg) enriched for production of suppressive proteins such as IL-10 and CTLA-4. However, these eTreg cells express the inhibitory receptor PD-1 and blockade of PD-L1 or loss of PD-1 results in increased eTreg cell activity associated with enhanced homeostatic proliferation and survival. Thus, eTreg cell expression of PD-1 acts as a sensor to rapidly tune the pool of eTreg cells at homeostasis.
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Project description:Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Tumor cell lysis by CTLs was attenuated when PD-L1 on tumor cells was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. Gene expression profile of mouse CTLs caused by PD-L1-overexpressing ovarian cancer was related to human CTLs exhaustion. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. Genome-wide transcriptional changes in OT-1 mouse CD8+ T cells that were co-incubated with OVA peptide-loaded ID8 mouse ovarian cancer cell lines. CTLs from 4 mice were devided into 2 groups, and co-incubated with PD-L1-overexpressed ID8 or PD-L1-depleted ID8.
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Project description:Although membrane-anchored Pd-l1 has been well-studied for its engagement with PD-1 on T cells to evade anti-tumor immunity, whether Pd-l1 regulate oncogenic signaling pathways in tumor cells remains elusive. In this experiment, to further dissect roles of the K262 residue acetylation for Pd-l1 nuclear function, we profiled RNA expression of WT or K262Q mutant mouse Pd-l1 re-expressed in CT26 KO Pd-l1 cells. Methods: Total RNA fromCT26/Vector, CT26/WT or CT26 Pd-l1 KO cells was purified using Qiagen RNeasy mini kit (Qiagen) according to the manufacturer’s instructions. Library preparation and sequenceing analysis were performed by BGI-Hong Kong Co. Ltd. Conclusions: Our study indicates that Pd-l1 acetylation modification may affect its function in nuclear.
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