Regulatory T cells in the treatment of disease

Sharabi, Amir; Tsokos, Maria; Ding, Ying; Malek, Thomas R.; Klatzmann, David; Tsokos, George C.

doi:10.1038/nrd.2018.148

Cited by 252 publications

(216 citation statements)

References 320 publications

(334 reference statements)

Supporting

Mentioning

212

Contrasting

Unclassified

Order By: Relevance

“…Beside Treg reprogramming, Treg cell depletion strategies have also been tested as anticancer therapy . In detail, monoclonal antibodies against CD25 have been used to kill Treg cells by antibody‐dependent cell‐mediated cytotoxicity and complement‐mediated cytotoxicity in preclinical and clinical studies alone and in combination with dendritic cell vaccines .…”

Section: Introductionmentioning

confidence: 99%

Blocking inflammation to improve immunotherapy of advanced cancer

Macciò

Madeddu

2019

Immunology

View full text Add to dashboard Cite

The ability to induce functional reprogramming of regulatory T (Treg) cells in the tumor microenvironment is an extremely important therapeutic opportunity. However, when discussing such an approach, the opposing effect that the activation of the Treg cell compartments may have in inducing the immune inflammatory response and its link with the efficacy of immunotherapy should be considered. In fact, Treg reprogramming has a dual effect: immediate, with mechanisms that activate immunosurveillance, and late, mediated by the macrophage activation that yields an inflammatory status that is deleterious for the antineoplastic efficiency of the immune system response. Persistence of the inflammatory response is associated with specific changes of oxidative and glycolytic metabolic pathways that interfere with conventional T‐cell activation and function and may be one of the reasons for the failure of immunotherapy in advanced cancer patients. Therefore, in addition to modulating Treg cell action, the combined use of drugs able to block chronic inflammation mediated mainly by macrophages, to counteract the oxidative stress, and to positively regulate the metabolic derangements, could improve the effectiveness of modern immunotherapy. In conclusion, reprogramming of Treg cells may be an appropriate strategy for treating early stages of neoplastic diseases, whereas other immunosuppressive mechanisms should be the target of a combined immunotherapy approach in more advanced phases of cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Blocking inflammation to improve immunotherapy of advanced cancer

Macciò

Madeddu

2019

Immunology

View full text Add to dashboard Cite

show abstract

“…Crohn's disease is mainly characterized by an enhanced Th1 response together with an increased Th17 immune response, which plays a critical role in the pathogenesis of CD . Local immune balance of intestinal tissue is maintained by regulatory T cells (Tregs) in the intestine that inhibit the proliferation and response of other helper‐T cells (Th cells) . Studies have indicated that CD is associated with impaired Treg responses and enhanced Th1/Th17 responses .…”

Section: Introductionmentioning

confidence: 99%

Spontaneous colitis in IL‐10‐deficient mice was ameliorated via inhibiting glutaminase1

Zuo

Tian

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Immunity imbalance and barrier damage in the intestinal mucosa are the main pathogenic factors of Crohn's disease (CD). Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide (BPTES) is a glutaminase 1 (Gls1) inhibitor with the dual functions of increasing glutamine levels and immune regulation. In this study, we focused on the role of BPTES in CD‐like enteritis and the possible mechanisms. We found that Gls1 expression was significantly increased in CD intestinal tissue compared with control tissue. Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide treatment significantly ameliorated chronic colitis in the IL‐10 −/− , as manifested by decreased disease activity index, body weight change, histological inflammatory degree and inflammatory cytokine expression. Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide treatment exerted protective effects on CD that were associated with the maintenance of intestinal barrier integrity and the Th/Treg balance. Bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl) ethyl sulfide treatment may act in part through TCR‐mediated mammalian target of rapamycin complex 1 (mTORC1) signalling activation. In conclusion, inhibition of Gls1 expression attenuated chronic colitis by maintaining intestinal barrier integrity and the Th/Treg balance, thereby ameliorating CD‐like colitis.

show abstract

“…These findings encourage to further evaluate circulating Tregs as a potential biomarker for treatment response. Furthermore, alternative therapeutic approaches modulating T‐cell metabolism, such as metformin, may improve the number and functions of Tregs, as showen in other clinical and pre‐clinical models of autoimmune diseases …”

Section: Discussionmentioning

confidence: 99%

Frequency of circulating subpopulations of T‐regulatory cells in patients with hidradenitis suppurativa

Hessam

Gambichler

Höxtermann

et al. 2019

Acad Dermatol Venereol

View full text Add to dashboard Cite

Background Decreased number of T‐regulatory cells (Tregs) and/or their loss of function potentially lead to uncontrolled immune‐mediated inflammatory responses. There are only few data available on Tregs in hidradenitis suppurativa (HS) – a disease in which it has been suggested that host immune factors and an overactive immune system of the follicular epithelium play a pathogenetic role. Objectives To analyse frequencies of Tregs subpopulations in blood of HS patients in comparison with a healthy control group. Materials & methods Blood samples obtained from HS patients and healthy controls were evaluated by flow cytometry and enzyme‐linked immunosorbent assay. Results The frequency of natural Tregs among CD4+ T lymphocytes were significantly reduced in the HS group compared to the healthy controls. The proportion of activated Tregs, non‐suppressive Tregs and proliferating Tregs showed no significant difference when compared to controls. Regarding Tregs frequencies, there was no significant difference between the three Hurley stages. Serum concentrations of IL‐10, TGF‐ß1 and IL‐17A did not show significant differences between the HS and control group. Conclusion The reduction of natural Tregs observed in blood of HS patients could be the result of Tregs homing to sites of inflammatory hot spots in HS skin. Further studies are justified evaluating the role of circulating Tregs during the evolution of HS lesions and as a biomarker for treatment response.

show abstract

Regulatory T cells in the treatment of disease

Cited by 252 publications

References 320 publications

Blocking inflammation to improve immunotherapy of advanced cancer

Blocking inflammation to improve immunotherapy of advanced cancer

Spontaneous colitis in IL‐10‐deficient mice was ameliorated via inhibiting glutaminase1

Frequency of circulating subpopulations of T‐regulatory cells in patients with hidradenitis suppurativa

Contact Info

Product

Resources

About