CD103+ cDC1 and endogenous CD8+ T cells are necessary for improved CD40L-overexpressing CAR T cell antitumor function

Kuhn, Nicholas F.; Lopez, Andrea V.; Li, Xinghuo; Winson, Cai; Daniyan, Anthony F.; Brentjens, Renier J.

doi:10.1038/s41467-020-19833-3

Cited by 26 publications

(17 citation statements)

References 49 publications

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“…4a). Additionally, the proportion of host CD103 + DCs in the graft (i.e., cells presumed to activate antigen-specific lymphocytes [29]), tended to be higher at 120 h than at 72 h (P = 0.09, Fig. 4b).…”

Section: Phenotypic Differences In Gils Were Observed Between 72 and 120 H Post-transplantationmentioning

confidence: 93%

Functional roles of graft‐infiltrating lymphocytes during early‐phase post‐transplantation in mouse cardiac transplantation models

Ganchiku

Goto

Kanazawa

et al. 2021

Transplant International

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Immunological behavior of graft-infiltrating lymphocytes (GILs) determines the graft fate (i.e., rejection or acceptance). Nevertheless, the functional alloreactivity and the phenotype of GILs at various times during the early post-transplantation phase have not been fully elucidated. We examined the immunological activities of early-phase GILs using a murine model of cardiac transplantation. GILs from 120-h allografts, but not 72-h allografts, showed robust activation and produced proinflammatory cytokines. In particular, a significant increase in CD69 + T-bet + Nur77 + T cells was detected in 120-h allografts. Furthermore, isolated GILs were used to reconstitute BALB/c Rag2 À/À cc À/À (BRG) mice. BRG mice reconstituted with 120-h GILs displayed donor-specific immune reactivity and rejected donor strain cardiac allografts; conversely, 72-h GILs exhibited weak antidonor reactivity and did not reject allografts. These findings were confirmed by re-transplantation of cardiac allografts into BRG mice at 72-h post-transplantation. Re-transplanted allografts continued to function for >100 days, despite the presence of CD3 + GILs. In conclusion, the immunological behavior of GILs considerably differs over time during the early post-transplantation phase. A better understanding of the functional role of early-phase GILs may clarify the fate determination process in the graftsite microenvironment.

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Section: Phenotypic Differences In Gils Were Observed Between 72 and 120 H Post-transplantationmentioning

confidence: 93%

Functional roles of graft‐infiltrating lymphocytes during early‐phase post‐transplantation in mouse cardiac transplantation models

Ganchiku

Goto

Kanazawa

et al. 2021

Transplant International

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“…CCL19 and CD40L are important DC chemoattractants. Engineered T cells with inserted CCL19 or CD40L can release these molecules, increasing the infiltration of DCs into tumors [ 353 , 354 ].…”

Section: Reprogramming Cell–cell Communicationmentioning

confidence: 99%

Reprogramming the tumor microenvironment by genome editing for precision cancer therapy

et al. 2022

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The tumor microenvironment (TME) is essential for immune escape by tumor cells. It plays essential roles in tumor development and metastasis. The clinical outcomes of tumors are often closely related to individual differences in the patient TME. Therefore, reprogramming TME cells and their intercellular communication is an attractive and promising strategy for cancer therapy. TME cells consist of immune and nonimmune cells. These cells need to be manipulated precisely and safely to improve cancer therapy. Furthermore, it is encouraging that this field has rapidly developed in recent years with the advent and development of gene editing technologies. In this review, we briefly introduce gene editing technologies and systematically summarize their applications in the TME for precision cancer therapy, including the reprogramming of TME cells and their intercellular communication. TME cell reprogramming can regulate cell differentiation, proliferation, and function. Moreover, reprogramming the intercellular communication of TME cells can optimize immune infiltration and the specific recognition of tumor cells by immune cells. Thus, gene editing will pave the way for further breakthroughs in precision cancer therapy.

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“…CD4 + T cells, also known as T helper cells (Th), recognize antigen/MHC-II complexes on antigen-presenting cells ( 42 ) and coordinate the activation of other immune cells, including B cells, macrophages. CD8 + cells, on the other hand, called T cytotoxic cells, recognize antigens/MHC-I complexes and are responsible for killing pathogen-infected cells ( 43 ). In healthy kidney tissue, T lymphocytes protect the kidney by performing a variety of biological functions to fight infection.…”

Section: Renal Microenvironmentmentioning

confidence: 99%

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives

Han

Tao

et al. 2022

Front. Immunol.

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Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

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CD103+ cDC1 and endogenous CD8+ T cells are necessary for improved CD40L-overexpressing CAR T cell antitumor function

Cited by 26 publications

References 49 publications

Functional roles of graft‐infiltrating lymphocytes during early‐phase post‐transplantation in mouse cardiac transplantation models

Functional roles of graft‐infiltrating lymphocytes during early‐phase post‐transplantation in mouse cardiac transplantation models

Reprogramming the tumor microenvironment by genome editing for precision cancer therapy

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives

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