Ectopic lymphoid tissues and local immunity

Carragher, Damian M.; Rangel-Moreno, Javier; Randall, Troy D.

doi:10.1016/j.smim.2007.12.004

Cited by 241 publications

(245 citation statements)

References 211 publications

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“…Second, in the absence of an assay to reliably define LTi cell function in vitro or in vivo, it is not possible to exclude the possibility that in mice with chronic Leishmania-induced inflammation, there may be RORγ-independent development of cells that can functionally compensate for classical LTi cells. In this regard, our data are compatible with reports that tertiary lymphoid structures can develop in an LTi cell-independent manner, particularly under inflammatory conditions (66,67).…”

Section: Discussionsupporting

confidence: 92%

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Dalton¹,

Maroof²,

Owens³

et al. 2010

J. Clin. Invest.

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Receptor tyrosine kinases are involved in multiple cellular processes, and drugs that inhibit their action are used in the clinic to treat several types of cancer. However, the value of receptor tyrosine kinase inhibitors (RTKIs) for treating infectious disease has yet to be explored. Here, we have shown in mice that administration of the broad-spectrum RTKI sunitinib maleate (Sm) blocked the vascular remodeling and progressive splenomegaly associated with experimental visceral leishmaniasis. Furthermore, Sm treatment restored the integrity of the splenic microarchitecture. Although restoration of splenic architecture was accompanied by an increase in the frequency of IFN-γ + CD4 + T cells, Sm treatment alone was insufficient to cause a reduction in tissue parasite burden. However, preconditioning by short-term Sm treatment proved to be successful as an adjunct therapy, increasing the frequency of IFN-γ + and IFN-γ + TNF + CD4 + T cells, enhancing NO production by splenic macrophages, and providing dose-sparing effects when combined with a first-line immune-dependent anti-leishmanial drug. We propose, therefore, that RTKIs may prove clinically useful as agents to restore immune competence before the administration of chemo-or immunotherapeutic drugs in the treatment of visceral leishmaniasis or other diseases involving lymphoid tissue remodeling, including cancer.

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Section: Discussionsupporting

confidence: 92%

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Dalton¹,

Maroof²,

Owens³

et al. 2010

J. Clin. Invest.

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“…It has, however, been reported that Tertiary Lymphoid Structures (TLS) are abundant in highly inflamed tissues resulting from chronic infections, auto-immune diseases or organ transplantation [38]. It has been demonstrated that efficient primary and secondary immune reactions can be generated in mice lacking lymph nodes [39,40].…”

Section: An Efficient Immune Reaction May Be Shaped At the Tumor Sitementioning

confidence: 99%

The Immune Microenvironment of Human Tumors: General Significance and Clinical Impact

Fridman

Dieu-Nosjean

Pagès

et al. 2012

Cancer Microenvironment

110

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Human cancers grow in a microenvironment of stromal, inflammatory and immunocompetent cells which is variable from tumor to tumor. The characterization of the immune contexture, i.e. the type, density and functional orientation of immunocompetent cells, the presence or absence of tertiary lymphoid structures is a major prognostic factor for patients survival and represent a guide and a target for innovative cancer therapies.

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“…Live in vivo two-photon imaging revealed that lymphocytes migrate into LNs and interact with antigen-presenting cells [69]. Tertiary lymphoid organs (TLOs), which can develop at sites of inflammation anywhere in the body, share the same function as SLOs [70] and are very similar in their organizational structure [71]. The successful engineering of artificial lymph node-like tertiary lymphoid organs (artTLOs) showed that these artificial structures are transplantable and retain their immunological function [72][73][74].…”

Section: Development Of Humanized Mouse Modelsmentioning

confidence: 99%

Chimeric Antigen Receptor T Cells for the Treatment of Cancer and the Future of Preclinical Models for Predicting their Toxicities

Wegner

2017

Immunotherapy

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CAR-T cell therapy has achieved highly promising results in clinical trials, particulary in B-cell malignancies. However, reports of Serious adverse events (SAE) including a number of patient deaths has raised concerns about safety of this treatment.Presently available pre-clinical models are not designed for predicting toxicities seen in human patients. Besides choosing the right animal model, careful considerations must be taken in CAR T-cell design and the amount of T-cells infused. The development of more sophisticated in vitro models and humanized mouse models for preclinical modeling and toxicity tests will help us to improve the design of clinical trials in cancer immunotherapy.

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Ectopic lymphoid tissues and local immunity

Cited by 241 publications

References 211 publications

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

The Immune Microenvironment of Human Tumors: General Significance and Clinical Impact

Chimeric Antigen Receptor T Cells for the Treatment of Cancer and the Future of Preclinical Models for Predicting their Toxicities

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