Treating ischemia via recruitment of antigen-specific T cells

Kwee, Brian J.; Seo, Bo Ri; Najibi, Alexander J.; Li, Aileen W.; Shih, Ting‐Yu; White, Des; Mooney, David J.

doi:10.1126/sciadv.aav6313

Cited by 31 publications

(31 citation statements)

References 45 publications

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“…Some T cell subsets participate in tissue repair and wound healing (152,153) and are useful for tissue engineering. For instance, the recruitment of antigen-specific T cells followed by Th2 adjuvant vaccination can help biomaterials for tissue repair (154). Studies on the influence of T cells on fibrosis are especially useful for the treatment of hypertrophic scarring, which is a severe form of fibrosis frequently developed in case of severe burn injuries.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

T Cells in Fibrosis and Fibrotic Diseases

2020

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Fibrosis is the extensive deposition of fibrous connective tissue, and it is characterized by the accumulation of collagen and other extracellular matrix (ECM) components. Fibrosis is essential for wound healing and tissue repair in response to a variety of triggers, which include infection, inflammation, autoimmune disorder, degenerative disease, tumor, and injury. Fibrotic remodeling in various diseases, such as liver cirrhosis, pulmonary fibrosis, renal interstitial fibrosis, myocardial infarction, systemic sclerosis (SSc), and graft-versus-host disease (GVHD), can impair organ function, causing high morbidity and mortality. Both innate and adaptive immunity are involved in fibrogenesis. Although the roles of macrophages in fibrogenesis have been studied for many years, the underlying mechanisms concerning the manner in which T cells regulate fibrosis are not completely understood. The T cell receptor (TCR) engages the antigen and shapes the repertoire of antigen-specific T cells. Based on the divergent expression of surface molecules and cell functions, T cells are subdivided into natural killer T (NKT) cells, γδ T cells, CD8 + cytotoxic T lymphocytes (CTL), regulatory T (Treg) cells, T follicular regulatory (Tfr) cells, and T helper cells, including Th1, Th2, Th9, Th17, Th22, and T follicular helper (Tfh) cells. In this review, we summarize the pro-fibrotic or anti-fibrotic roles and distinct mechanisms of different T cell subsets. On reviewing the literature, we conclude that the T cell regulations are commonly disease-specific and tissue-specific. Finally, we provide perspectives on microbiota, viral infection, and metabolism, and discuss the current advancements of technologies for identifying novel targets and developing immunotherapies for intervention in fibrosis and fibrotic diseases.

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Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

T Cells in Fibrosis and Fibrotic Diseases

2020

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“…118,119 The normalised tumour vasculature and CD4 + T H 1 cell immune response create some sort of positive feedback loop that generates a controlled angiogenic response. 120,121 LESSONS FROM GLIOBLASTOMA In a clinical study in which glioblastoma patients were given a single dose of AZD2171 (cediranib, a VEGFR inhibitor) signs of vessel normalisation-based on the calculation of a 'vascular normalisation index'-lasted for as long as 28 days, with some features of the normalised network persisting for up to 4 months. Vascular permeability/flow and microvessel volume assessed by fMRI correlated positively with the clinical outcome of patients with glioblastoma.…”

Section: Vascular Normalisation Anti-cancer Treatment and The Tmementioning

confidence: 99%

Vascular normalisation as the stepping stone into tumour microenvironment transformation

Magnussen

Mills

2021

Br J Cancer

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A functional vascular system is indispensable for drug delivery and fundamental for responsiveness of the tumour microenvironment to such medication. At the same time, the progression of a tumour is defined by the interactions of the cancer cells with their surrounding environment, including neovessels, and the vascular network continues to be the major route for the dissemination of tumour cells in cancer, facilitating metastasis. So how can this apparent conflict be reconciled? Vessel normalisation—in which redundant structures are pruned and the abnormal vasculature is stabilised and remodelled—is generally considered to be beneficial in the course of anti-cancer treatments. A causality between normalised vasculature and improved response to medication and treatment is observed. For this reason, it is important to discern the consequence of vessel normalisation on the tumour microenvironment and to modulate the vasculature advantageously. This article will highlight the challenges of controlled neovascular remodelling and outline how vascular normalisation can shape disease management.

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“…The angiogenic and arteriogenic potency of monocytes is well described [17,18,20,21,54]. More recently several studies also indicate an angiogenic function of speci c limphocytes populations [25,[55][56][57][58].…”

Section: Discussionmentioning

confidence: 93%

The use of Peripheral Blood-Mononuclear Cells in Scleroderma patients: an observational preliminary study

Carella

Rossi

Ribuffo

et al. 2020

Preprint

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Background Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy and excessive production of collagen, which lead to skin and visceral fibrosis. The aim of our study is to assess the potential benefits of peripheral blood mononuclear cells (PB-MNCs) implants in the treatment of clinical manifestations such as mouth impairment, hand disability, digital ulcers and Raynaud’s phenomenon in Scleroderma patients. Methods From February 2016 to May 2019, 10 female patients were enrolled from the outpatient clinic of the Plastic Surgery Unit of Sapienza University of Rome. Parameters evaluated were: patients’ disability, using the Health Assessment Questionnaire (HAQ) disability index (DI) and the scleroderma HAQ (sHAQ); mouth opening capacity, by measuring the maximum interincisal distance and the mouth perimeter; hand mobility, assessed with clinical exam and the Hand Mobility in Scleroderma (HAMIS) scale; Raynaud’s phenomenon, evaluated through nailfold capillaroscopy; digital ulcers, examined through their features and incidence of appearance. SPSS software was used for a simple descriptive statistical analysis performed by the Student's paired t-test. P values less than 0.05 were considered statistically significant. Results The treatment showed a significant improvement of all the parameters evaluated at 1-year follow-up, it was well-tolerated by all the patients and the only complications noticed were small areas of ecchymosis. Conclusions Our results suggest that PB-MNCs injection could represent a treatment option to take into account for SSc patients. The procedure we used is easy and fast to perform, minimally invasive and not-operator dependent. We hope our observational and preliminary study could be considered as a starting point for further research studies.

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Treating ischemia via recruitment of antigen-specific T cells

Cited by 31 publications

References 45 publications

T Cells in Fibrosis and Fibrotic Diseases

T Cells in Fibrosis and Fibrotic Diseases

Vascular normalisation as the stepping stone into tumour microenvironment transformation

The use of Peripheral Blood-Mononuclear Cells in Scleroderma patients: an observational preliminary study

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