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Last update 08 May 2025

GITRL

Last update 08 May 2025

Basic Info

Synonyms

Activation-inducible TNF-related ligand, AITRL, GITRL

+ [6]

Introduction

Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T-cell responses. Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation. Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B. Triggers increased phosphorylation of STAT1 and up-regulates expression of VCAM1 and ICAM1 (PubMed:23892569). Promotes leukocyte adhesion to endothelial cells (PubMed:23892569). Regulates migration of monocytes from the splenic reservoir to sites of inflammation (By similarity).

Drugs associated with GITRL

Delta-24-GREAT

Target

GITRL

Mechanism

GITRL modulators

Active Org.

The University of Texas MD Anderson Cancer Center

Originator Org.

The University of Texas MD Anderson Cancer Center

Active Indication

Glioma

Inactive Indication

Metastatic breast cancer

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GITRL

100 Translational Medicine associated with GITRL

0 Patents (Medical) associated with GITRL

267

Literatures (Medical) associated with GITRL

01 Feb 2025·Translational Oncology

Cellular heterogeneity and cytokine signatures in acute myeloid leukemia: A novel prognostic model

Article

Author: Fang, Dan ; Jiang, Ling ; Li, Tianqi ; Cao, Jinxia ; Wang, Jun ; Hu, Bin

Acute Myeloid Leukemia (AML) is a complex hematological malignancy distinguished by its heterogeneity in genetic aberrations, cellular composition, and clinical outcomes. This diversity complicates the development of effective, universally applicable therapeutic strategies and highlights the necessity for personalized approaches to treatment. In our study, we utilized high-resolution single-cell RNA sequencing from publicly available datasets to dissect the complex cellular landscape of AML. This approach uncovered a diverse array of cellular subpopulations within the bone marrow samples of AML patients. Through meticulous analysis, we identified 156 differentially expressed cytokine-related genes that underscore the nuanced interplay between AML cells and their microenvironment. Leveraging this comprehensive dataset, we constructed a prognostic risk score model based on seven pivotal cytokine-related genes: CCL23, IL2RA, IL3RA, IL6R, INHBA, TNFSF15, and TNFSF18. The mRNA levels of 7 genes in the risk score model have significant different. This model was rigorously validated across several independent AML patient cohorts, showcasing its robust prognostic capability to stratify patients into distinct risk categories. Patients classified under the high-risk category exhibited significantly poorer survival outcomes compared to their low-risk counterparts, underscoring the model's clinical relevance. Additionally, our in-depth investigation into the immune landscape revealed marked differences in immune cell infiltration and cytokine signaling between the identified risk groups, shedding light on potential immune-mediated mechanisms driving disease progression and treatment resistance. This comprehensive analysis not only advances our understanding of the cellular and molecular underpinnings of AML but also introduces a novel, clinically applicable risk score model. This tool holds significant promise for enhancing the precision of prognostic assessments in AML, thereby paving the way for more tailored and effective therapeutic interventions. Our findings represent a pivotal step toward the realization of personalized medicine in the management of AML, offering new avenues for research and treatment optimization in this challenging disease landscape.

21 Jan 2025·ACS Nano

Maternal Exposure to Polystyrene Nanoplastics Disrupts Spermatogenesis in Mouse Offspring by Inducing Prdm14 Overexpression in Undifferentiated Spermatogonia

Article

Author: Huang, Qixian ; Zhan, Dian ; Li, Sisi ; Wang, Lirui ; Jiang, Shengyao ; Li, Xinhong ; Ma, Sheng ; Xiong, Manyi ; Kui, Haozhan ; Jiang, Yanping

Undifferentiated spermatogonia (Undiff-SPG) plays a critical role in maintaining continual spermatogenesis. However, the toxic effects and molecular mechanisms of maternal exposure to nanoplastics on offspring Undiff-SPG remain elusive. Here, we utilized a multiomics combined cytomorphological approach to explore the reproductive toxicity and mechanisms of polystyrene nanoplastics (PS-NPs) on offspring Undiff-SPG in mice after maternal exposure. The results indicated that PS-NPs decreased testosterone levels and reduced sperm concentration and quality in offspring male mice through maternal exposure. Moreover, PS-NPs could enter offspring Undiff-SPG, increase ROS levels, and decrease the viability of Undiff-SPG. According to the transcriptomics and proteomics analyses, PS-NPs caused offspring male mice Undiff-SPG inflammation by increasing the expression of Tnfsf18/Nlrp6. Mechanistically, we found that inflammation induced overexpression of the transcription factor Prdm14 in Undiff-SPG, which suppressed the expression of Ccdc33 and Tcirg1. Additionally, PS-NPs disrupted offspring spermatogenesis by inhibiting the Osbp2/Zcwpw1/Dhps expression. Furthermore, PS-NPs reduced the Undiff-SPG autophagic flux by reducing the expression of Igbp1/Gabarapl2. In conclusion, maternal exposure to PS-NPs caused inflammation in offspring Undiff-SPG, which resulted in Prdm14 overexpression that could disrupt spermatogenesis and normal autophagy.

01 Jan 2025·Molecular Therapy

GITRL enhances cytotoxicity and persistence of CAR-T cells in cancer therapy

Article

Author: Liu, Mingyao ; Du, Bing ; Zhang, Na ; Xiong, Hao ; Lin, Boxu ; Qin, Juliang ; Xu, Yongqian ; Tu, Chuntian ; Tan, Binghe ; Yang, Ruijie ; Zhang, Xiaolin ; Shi, Xiujuan

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and the limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of GITR ligand enhances the anti-tumor activity of CAR-T cells. Compared to prostate-specific membrane antigen-BB-Z (PSMA-BB-Z) CAR-T, PSMA-BB-Z-GITRL CAR-T cells have much more interferon (IFN)-γ, TNF-α, and interleukin (IL)-9 secretion, a higher proportion of central memory T (T_CM) cells and T helper 9 (Th9) cells, less expression of exhaustion markers, and robust proliferation capacity. Consequently, PSMA-BB-Z-GITRL CAR-T cells exhibited more potent anti-tumor activity against established solid tumors in vivo than PSMA-BB-Z CAR-T cells. The results of the in vivo persistence experiment also indicated that PSMA-BB-Z-GITRL CAR-T cells exhibited much more retention in mouse blood, spleen, and tumor tissue than PSMA-BB-Z CAR-T cells 15 days after CAR-T cell therapy. In addition, PSMA-BB-Z-GITRL CAR-T cells produce higher levels of IFN-γ, TNF-α, and IL-9 in mouse blood, exhibiting a higher proportion of T_CM cells and a lower proportion of Treg cells compared to PSMA-BB-Z CAR-T cells. Our results demonstrate that the overexpression of GITRL has important implications for improving CAR-T cell-based human solid tumor immunotherapy.

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