Recruitment and Activation of Naive T Cells in the Islets by Lymphotoxin β Receptor-Dependent Tertiary Lymphoid Structure

Lee, Youjin; Chin, Robert; Christiansen, Peter A.; Sun, Yonglian; Tumanov, Alexei V.; Wang, Jing H.; Chervonsky, Alexander V.; Fu, Yang–Xin

doi:10.1016/j.immuni.2006.06.016

Cited by 144 publications

(150 citation statements)

References 46 publications

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“…baminercept and pateclizumab) may prove effective in blocking ELF activity. Although clinically untested for ELF‐associated inflammation, targeting LT β has shown promise in pre‐clinical experimental models of disease 126, 127, 128, 129. Similarly, CXCL13 blockade has shown some promise in pre‐clinical studies for the treatment of experimental inflammatory arthritis, diabetes and Sjögren syndrome 130, 131, 132.…”

Section: Concluding Remarks and Future Perspectives On The Therapeutimentioning

confidence: 99%

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

2015

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SummaryLymphoid neogenesis is traditionally viewed as a pre‐programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen‐specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto‐immunity, transplantation, cancer or environmental irritants. Although these structures affect local immune responses, the contribution of these lymphoid aggregates to the underlining pathology are highly context dependent and can elicit either protective or deleterious outcomes. Here we review the cellular and molecular mechanisms responsible for ectopic lymphoid neogenesis and consider the relevance of these structures in human disease.

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Section: Concluding Remarks and Future Perspectives On The Therapeutimentioning

confidence: 99%

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

2015

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“…Comparable to anti-tumor immunity, it is often observed in murine autoimmune models that the presence of autoreactive cells alone is not sufficient to cause tissue destruction [21]. It has been reported recently that the organized tertiary lymphoid structure (TLS) is necessary and sufficient to induce autoimmune destruction of pancreatic islets [22]. Indeed, de novo organization of TLS is known to precede the development of a number of human autoimmune diseases [23,24].…”

Section: Light Creates Lymphoid-like Tissues Inside the Tumor To Imprmentioning

confidence: 99%

“…In vivo data demonstrate that LIGHT mediates development of a microenvironment sufficient to break immunological tolerance to self antigens. First, ectopic expression of LIGHT in the pancreatic islets resulted in the formation of lymphoid-like structures and was necessary and sufficient for pancreatic islet destruction [22]. In addition, sustained expression of LIGHT on T cells leads to their activation, migration into peripheral tissues, and the establishment of lymphoidlike structures in situ [38,39].…”

Section: Light Creates Lymphoid-like Tissues Inside the Tumor To Imprmentioning

confidence: 99%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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Metastastic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor superfamily member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells, NK cells, naïve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin β receptor (LTβR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.

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“…It has been reported recently that the organized tertiary lymphoid structure (TLS) is necessary and sufficient to induce autoimmune destruction of pancreatic islets. 46 Indeed, de novo organization of a TLS is known to precede the development of a number of human autoimmune diseases and animal models. 47,48 These observations suggest that lymphoid neogenesis within the target tissue may have a critical role in initiating and maintaining immune responses against persistent antigens.…”

Section: Targeted Immunotherapy To Primary Tumor Tissues Can Generatementioning

confidence: 99%

“…First, ectopic expression of LIGHT in the pancreatic islets resulted in the formation of lymphoid-like structures, and was necessary and sufficient for pancreatic islet destruction. 46 In addition, sustained expression of LIGHT on T cells leads to their activation, migration into peripheral tissues and the establishment of lymphoid-like structures in situ. 66,67 LIGHT also acts as a strong costimulatory molecule for T-cell activation, possibly by binding to the herpesvirus entry mediator on T cells.…”

Section: Targeted Immunotherapy To Primary Tumor Tissues Can Generatementioning

confidence: 99%

Targeting and utilizing primary tumors as live vaccines: changing strategies

Yang

Mortenson

2011

Cell Mol Immunol

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Tumor metastases and relapse are the major causes of morbidity and mortality in cancer. Although surgery, chemotherapy and/or radiation therapy can typically control primary tumor growth, metastatic and relapsing tumors are often inaccessible or resistant to these treatments. An adaptive immune response can be generated during these conventional treatments of the primary tumor, and presumably both the primary tumor and secondary metastases share many of the same or similar antigenic characteristics recognized by the immune system. Thus, when established, this response should be able to control metastatic growth and tumor relapse. This review summarizes the mechanisms by which antitumor immune responses are generated, and recent findings supporting the hypothesis that many therapies targeting primary tumors can generate antitumor adaptive immune responses to prevent metastases and tumor relapse. Keywords: chemotherapy; immunotherapy; metastasis; radiotherapy; tumor vaccine INTRODUCTION Conventional treatments such as surgery and chemotherapy are effective means of eliminating or reducing primary tumor growth, but have not proved effective in eradicating metastases. Because metastatic disease may not respond similarly to chemotherapies used in treating the primary tumor, 1 recent research has focused on the importance of generating an antitumor immune response to control metastatic disease. Presumably, both the primary tumor and secondary metastases share many of the same or similar antigenic characteristics recognized by the immune system; yet, there has been no clear strategy formulated in which a patient's own tumor tissues is used to generate an antitumor adaptive immune response for the eradication of metastases and prevention of relapse. Once tumors metastasize, curing the disease is difficult and rare. This review summarizes recent findings supporting the hypothesis that targeting primary tumors with both conventional and new therapies can potentially generate antitumor adaptive immune responses that prevent metastases and relapse.Due to the vast number of genetic changes associated with carcinogenesis, tumors express many neo-antigens and mutated antigens. Indeed, much evidence exists to indicate that many cancers are antigenic and thus recognizable by the adaptive immune system. 2 Mere recognition by adaptive immunity, however, is insufficient, given that these antigenic cancers rarely regress spontaneously. Effective antitumor immunity depends on both the presence of tumor-reactive lymphocyte precursors and means by which these precursor lymphocytes can be activated. Most T cells with high affinity to tissue-specific antigens are deleted in the thymus or later tolerized in the peripheral

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Recruitment and Activation of Naive T Cells in the Islets by Lymphotoxin β Receptor-Dependent Tertiary Lymphoid Structure

Cited by 144 publications

References 46 publications

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Targeting and utilizing primary tumors as live vaccines: changing strategies

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