Blockade of PD-1/PD-L1 increases effector T cells and aggravates murine chronic graft-versus-host disease

Liang, Yiqing; Shen, Jingyi; Qiu, Lan; Zhang, Kexin; Xu, Yan; Duah, Maxwell; Xu, Kailin; Pan, Bin

doi:10.1016/j.intimp.2022.109051

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…174,[306][307][308] Furthermore, enhancing the function of effector T lymphocytes to reverse the suppressive effect of Tregs has also been used in tumor immunotherapy. 309 These ligands, which act as a brake for T lymphocytes, mainly induce TILs involved in antitumor immunity that fail to eliminate osteosarcoma cells, while related inhibitors can enhance T lymphocyteinduced antitumor immunity by MHC presentation to overcome obstacles and reverse this process. 310,311 Notably, strategies aimed at the novel targets PD-1 and CTLA-4 represent a new era of antitumor immunotherapy and improve the potential for osteosarcoma therapy.…”

Section: Immune Checkpoint Blockade-based Immunotherapy For Osteosarcomamentioning

confidence: 99%

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Tian

Cao

et al. 2023

Bone Res

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Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

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Section: Immune Checkpoint Blockade-based Immunotherapy For Osteosarcomamentioning

confidence: 99%

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Tian

Cao

et al. 2023

Bone Res

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“…In addition, several studies regarding the PD-1 pathway in other transplantations, including skin, liver, islet, and allogeneic hematopoietic stem cells, have also been reported ( 91 , 100 – 102 ). Mechanistically, PD-1 and its ligands, PD-L1 and PD-L2, constitute an inhibitory regulatory pathway with potential therapeutic use in transplanted organs undergoing allograft rejection ( 92 ).…”

Section: Transplantation Immunitymentioning

confidence: 99%

“…Immune checkpoints are crucial regulators of the immune system for self-tolerance and the prevention of rejection in the context of transplantation. To date, PD-1 and its ligands have been reported to play a significant role in the balance between reactive T cells targeting the organ and tolerogenic Tregs (59,(91)(92)(93). Upregulation of PD-1, PD-L1, and PD-L2 in a murine model of cardiac transplantation during the process of allogeneic rejection was observed compared with that in syngeneic transplants and normal tissues (94).…”

Section: Transplantation Immunitymentioning

confidence: 99%

The role of PD-1 signaling in health and immune-related diseases

et al. 2023

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Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.

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Aryl hydrocarbon receptor regulates IL-22 receptor expression on thymic epithelial cell and accelerates thymus regeneration

Shen,

Wang,

Zheng

et al. 2023

npj Regen Med

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Improving regeneration of damaged thymus is important for reconstituting T-cell immunity. Interleukin-22 (IL-22) was proved to improve thymus regeneration through recovering thymic epithelial cells (TECs). The IL-22 receptor IL-22RA1 is crucial for mediating IL-22 functions. Mechanism that regulates IL-22RA1 expression is unknown. Through using TECs-conditional knockout mice, we found aryl hydrocarbon receptor (AHR) is important for thymus regeneration, because Foxn1-cre-mediated AHR knockout (AhrKO) significantly blocks recovery of thymus cells. Giving mice the AHR inhibitor CH-223191 or the AHR agonist FICZ blocks or accelerates thymus regeneration, respectively. AhrKO-mediated blockade of thymus regeneration could not be rescued by giving exogenous IL-22. Mechanistically, AhrKO mice shows decreased IL-22RA1 expression. In the murine TECs cell line mTEC1 cells, targeting AHR shows an impact on IL-22RA1 mRNA levels. Using chromatin immunoprecipitation and luciferase reporter assays, we find AHR co-operates with STAT3, binds the promotor region of IL-22RA1 gene and transcriptionally increases IL-22RA1 expression in mTEC1 cells. Foxn1-cre-mediated IL-22RA1 knockout (Il22ra1KO) blocks thymus regeneration after irradiation. Furthermore, targeting AHR or IL-22RA1 has significant impacts on severity of murine chronic graft-versus-host disease (cGVHD), which is an autoimmune-like complication following allogeneic hematopoietic cell transplantation. Giving FICZ decreases cGVHD, whereas Il22ra1KO exacerbates cGVHD. The impacts on cGVHD are associated with thymus regeneration and T-cell immune reconstitution. In conclusion, we report an unrecognized function of TECs-expressed AHR in thymus regeneration and AHR transcriptionally regulates IL-22RA1 expression, which have implications for improving thymus regeneration and controlling cGVHD.

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Blockade of PD-1/PD-L1 increases effector T cells and aggravates murine chronic graft-versus-host disease

Cited by 5 publications

References 32 publications

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

The role of PD-1 signaling in health and immune-related diseases

Aryl hydrocarbon receptor regulates IL-22 receptor expression on thymic epithelial cell and accelerates thymus regeneration

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