scholarly journals Insights Into Unveiling a Potential Role of Tertiary Lymphoid Structures in Metastasis

2021 ◽  
Vol 8 ◽  
Author(s):  
Rami Mustapha ◽  
Kenrick Ng ◽  
James Monypenny ◽  
Tony Ng
Keyword(s):  
Antitumor Immunity ◽  
Cancer Metastasis ◽  
Potential Role ◽  
Cancer Invasiveness ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures ◽  
Cancer Dissemination ◽  
Alternative Routes ◽  
Biomechanical Factors

Tertiary lymphoid structures (TLSs) develop in non-lymphatic tissue in chronic inflammation and cancer. TLS can mature to lymph node (LN) like structures with germinal centers and associated vasculature. TLS neogenesis in cancer is highly varied and tissue dependent. The role of TLS in adaptive antitumor immunity is of great interest. However, data also show that TLS can play a role in cancer metastasis. The importance of lymphatics in cancer distant metastasis is clear yet the precise detail of how various immunosurveillance mechanisms interplay within TLS and/or draining LN is still under investigation. As part of the tumor lymphatics, TLS vasculature can provide alternative routes for the establishment of the pre-metastatic niche and cancer dissemination. The nature of the cytokine and chemokine signature at the heart of TLS induction can be key in determining the success of antitumor immunity or in promoting cancer invasiveness. Understanding the biochemical and biomechanical factors underlying TLS formation and the resulting impact on the primary tumor will be key in deciphering cancer metastasis and in the development of the next generation of cancer immunotherapeutics.

scholarly journals Divergent cancer etiologies drive distinct B cell signatures and tertiary lymphoid structures

2020 ◽  
Author(s):  
Ayana T Ruffin ◽  
Anthony R Cillo ◽  
Tracy Tabib ◽  
Angen Liu ◽  
Sayali Onkar ◽  
...  
Keyword(s):  
B Cells ◽  
Single Cell ◽  
Antitumor Immunity ◽  
Spatial Organization ◽  
Environmental Carcinogens ◽  
Transitional State ◽  
Rnaseq Data ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

AbstractCurrent immunotherapy paradigms aim to reinvigorate CD8+ T cells, but the contribution of humoral immunity to antitumor immunity remains understudied1,2. Head and neck squamous cell carcinoma (HNSCC) is caused by either human papillomavirus (HPV+) or environmental carcinogens (i.e. tobacco and alcohol; HPV–)3,4. Here, we demonstrate that HPV+ HNSCC patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with GC-like tertiary lymphoid structures (TLS), both of which correlate with favorable outcomes in HNSCC patients. Further, our single-cell RNAseq data also indicate that GC TIL-Bs are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. High-dimensional spectral flow cytometry permitted in depth characterization of activated, memory and GC TIL-Bs. Further, single cell RNAseq analysis and subsequent protein validation identified a role for semaphorin 4a (Sema4a) in the differentiation of GC TIL-Bs and indicated that expression of Sema4a was enhanced on GC TIL-Bs and within GC-like TLS in the TME. Thus, in contrast to some reports on the detrimental role of TIL-Bs in human tumors, our findings suggest that TIL-Bs play an instrumental role in antitumor immunity5,6. Novel therapeutics to enhance TIL-B responses in HNSCC should be prioritized as a compliment to current T-cell mediated immunotherapies.

scholarly journals Tertiary Lymphoid Structures in Cancer: The Double-Edged Sword Role in Antitumor Immunity and Potential Therapeutic Induction Strategies

2021 ◽  
Vol 12 ◽  
Author(s):  
Wendi Kang ◽  
Zhichao Feng ◽  
Jianwei Luo ◽  
Zhenhu He ◽  
Jun Liu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Antitumor Immunity ◽  
Close Association ◽  
Germinal Centers ◽  
Vital Role ◽  
Cancer Development ◽  
Multiple Strategies ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

The complex tumor microenvironment (TME) plays a vital role in cancer development and dramatically determines the efficacy of immunotherapy. Tertiary lymphoid structures (TLSs) within the TME are well recognized and consist of T cell-rich areas containing dendritic cells (DCs) and B cell-rich areas containing germinal centers (GCs). Accumulating research has indicated that there is a close association between tumor-associated TLSs and favorable clinical outcomes in most types of cancers, though a minority of studies have reported an association between TLSs and a poor prognosis. Overall, the double-edged sword role of TLSs in the TME and potential mechanisms need to be further investigated, which will provide novel therapeutic perspectives for antitumor immunoregulation. In this review, we focus on discussing the main functions of TLSs in the TME and recent advances in the therapeutic manipulation of TLSs through multiple strategies to enhance local antitumor immunity.

Exploring the Role of Tertiary Lymphoid Structures Using a Mouse Model of Bacteria-Infected Lungs

2018 ◽  
pp. 223-239 ◽  
Author(s):  
Jean-Luc Teillaud ◽  
Lucile Regard ◽  
Clémence Martin ◽  
Sophie Sibéril ◽  
Pierre-Régis Burgel
Keyword(s):  
Mouse Model ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

scholarly journals Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology

2019 ◽  
Vol 116 (27) ◽  
pp. 13490-13497 ◽  
Author(s):  
Saba Nayar ◽  
Joana Campos ◽  
Charlotte G. Smith ◽  
Valentina Iannizzotto ◽  
David H. Gardner ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Functional Role ◽  
Functional Requirements ◽  
Local Production ◽  
Functional Changes ◽  
Molecular Programming ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.

Role of intratumoral tertiary lymphoid structures as key modulators in the antitumor immune response in pancreatic cancer

Pancreatology ◽  
2020 ◽  
Vol 20 ◽  
pp. S125
Author(s):  
C. Mota Reyes ◽  
R. Istvanffy ◽  
O. Safak ◽  
B. Konukiewitz ◽  
A. Muckenhuber ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Response ◽  
Antitumor Immune Response ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Abstract A124: Tertiary lymphoid structures: Predictors of effective antitumor immunity in human breast cancer?

2016 ◽  
Author(s):  
Soizic Garaud ◽  
Laurence Buisseret ◽  
Chunyan Gu-Trantien ◽  
Gert Van den Eynden ◽  
Alexandre de Wind ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Antitumor Immunity ◽  
Human Breast ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Crystal structure of the FAS1 domain of the hyaluronic acid receptor stabilin-2

2018 ◽  
Vol 74 (7) ◽  
pp. 695-701 ◽  
Author(s):  
Aleksandra Twarda-Clapa ◽  
Beata Labuzek ◽  
Dobroslawa Krzemien ◽  
Bogdan Musielak ◽  
Przemyslaw Grudnik ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Cancer Metastasis ◽  
Potential Role ◽  
Three Dimensional ◽  
Protein Fragments ◽  
Acid Receptor ◽  
X Ray ◽  
Insight Into

Recent research has identified a potential role of the hyaluronic acid receptor stabilin-2 (Stab2) in cancer metastasis. Stab2 belongs to a group of scavenger receptors and is responsible for the clearance of more than ten ligands, including hyaluronic acid (HA). In vivo experiments on mice have shown that the absence of Stab2, or its blocking by an antibody, effectively opposes cancer metastasis, which is accompanied by an increase in the level of circulating HA. Knowledge of ligand recognition and signal transduction by Stab2 is limited and no three-dimensional structures of any protein fragments of this receptor have been solved to date. Here, a high-resolution X-ray structure of the seventh FAS1 domain of Stab2 is reported. This structure provides the first insight into the Stab2 structure.

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