Tertiary lymphoid structures in cancer and beyond

Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolás A.; Fridman, Wolf‐Herman

doi:10.1016/j.it.2014.09.006

Cited by 441 publications

(424 citation statements)

References 82 publications

(151 reference statements)

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“…However, there is emerging appreciation that during chronic inflammation, infiltrating immune cells can form highly organized aggregates of lymphoid cells that resemble SLOs. These ectopic lymphoid follicles (ELFs), also known as tertiary lymphoid structures, can propagate local antigen‐specific responses within tissues 9, 10. Occasionally, these ELFs are named according to their site of development (e.g.…”

Section: Secondary and Ectopic Lymphoid Organsmentioning

confidence: 99%

“…The expression of homeostatic chemokines is increased in tissues where ELFs have emerged in response to foreign or auto antigens 1, 9, 10, 12. Chemokines such as CXCL13, CCL19, CCL21 and CXCL12 are involved not only in the initiation of ELF development, but also in the maintenance of the highly organized cellular architecture of established ELFs and SLOs.…”

Section: Homeostatic Chemokines In Elf Developmentmentioning

confidence: 99%

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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: Secondary and Ectopic Lymphoid Organsmentioning

confidence: 99%

Section: Homeostatic Chemokines In Elf Developmentmentioning

confidence: 99%

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

2015

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“…5,29 Though the presence and density of TLOs have been found to correlate with better patient outcomes across tumour types, 4 further investigation into their mechanism of antitumour immunity as well as drivers of their formation is warranted. In particular, the role that TLO B cells play in anti-tumour immunity has been understudied.…”

Section: Discussionmentioning

confidence: 99%

“…4 In addition to sites of chronic infection and autoimmune disease, TLOs have been detected in a range of solid cancer types, including lung, breast, colorectal, and skin, where they mediate antitumour immunity via CD8 + T cell and antibody-based cytotoxicity. 4 The presence and density of TLOs correlate with favourable patient outcome in the vast majority of primary and metastatic tumours investigated, though the role of TLO-specific Tfh remains poorly defined. 4 …”

Section: Introductionmentioning

confidence: 99%

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Somatic mutation-associated T follicular helper cell elevation in lung adenocarcinoma

Marshall

Enfield

et al. 2018

OncoImmunology

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T follicular helper cells (Tfh) play crucial roles in the development of humoral immunity. In the B cell-rich germinal center of lymphoid organs, they select for high-affinity B cells and aid in their maturation. While Tfh have known roles in B cell malignancies and have prognostic value in some epithelial cancers, their role in lung tumour initiation and development is unknown. Through immune cell deconvolution, we observed significantly increased Tfh in tumours from two independent cohorts of lung adenocarcinomas and found that this upregulation occurs early in tumour development. A subset of tumours were stained for T and B cells using multicolour immunohistochemistry, which revealed the presence of tumour-adjacent tertiary lymphoid organs in 17/20 cases each with an average of 16 Tfh observed in the germinal center. Importantly, Tfh levels were correlated with tumour mutational load and immunogenic cancer testis antigens, suggesting their involvement in mounting an active immune response against tumour neoantigens.

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Rapid Generation of hPSC‐Derived High Endothelial Venule Organoids with In Vivo Ectopic Lymphoid Tissue Capabilities

Wang,

Li,

Zhao

et al. 2024

Advanced Materials

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Bioengineering strategies for the fabrication of implantable lymphoid structures mimicking lymph nodes (LNs) and tertiary lymphoid structures (TLS) could amplify the adaptive immune response for therapeutic applications such as cancer immunotherapy. No method to date has resulted in the consistent formation of high endothelial venules (HEVs), which is the specialized vasculature responsible for naïve T cell recruitment and education in both LNs and TLS. Here we used orthogonal induced differentiation of human pluripotent stem cells (hPSCs) carrying a regulatable ETV2 allele, to rapidly and efficiently induce endothelial differentiation. Assembly of embryoid bodies combining primitive inducible endothelial cells (iEndos) and primary human lymph node fibroblastic reticular cells (FRCs) resulted in the formation of HEV‐like structures that can aggregate into three dimensional organoids (HEVOs). Upon transplantation into immunodeficient mice, HEVOs successfully engrafted and formed lymphatic structures that recruited both antigen‐presenting cells and adoptively‐transferred lymphocytes, therefore displaying basic TLS capabilities. Our results further show that functionally, HEVOs can organize an immune response and promote anti‐tumor activity by adoptively transferred T lymphocytes. Collectively, our experimental approaches represent an innovative and scalable proof‐of‐concept strategy for the fabrication of bioengineered tertiary lymphoid structures that can be deployed in vivo to enhance adaptive immune responses.This article is protected by copyright. All rights reserved

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Tertiary lymphoid structures in cancer and beyond

Cited by 441 publications

References 82 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

Somatic mutation-associated T follicular helper cell elevation in lung adenocarcinoma

Rapid Generation of hPSC‐Derived High Endothelial Venule Organoids with In Vivo Ectopic Lymphoid Tissue Capabilities

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