scholarly journals IL-1α secreted by subcapsular sinus macrophages promotes melanoma metastasis in the sentinel lymph node by upregulating STAT3 signaling in the tumor.

2021 ◽  
Author(s):  
Tommaso Virgilio ◽  
Joy Bordini ◽  
Giulio Sartori ◽  
Irene Latino ◽  
Daniel Molina-Romero ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Tumor Antigens ◽  
Inflammatory Responses ◽  
Lymphatic Vessels ◽  
The Body ◽  
Melanoma Metastasis ◽  
Metastatic Cells ◽  
Subcapsular Sinus ◽  
Metastatic Microenvironment

During melanoma metastasization, tumor cells originated in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN) in a process that facilitates their spread across the body. Here, we characterized the innate inflammatory responses to melanoma metastasis in the sLN. For this purpose, we confirmed the migration of fluorescent metastatic melanoma cells to the sLN and we characterized the inflammatory response in the metastatic microenvironment. We found that macrophages located in the subcapsular sinus (SSM), produce pro-tumoral IL-1α after recognition of tumor antigens. Moreover, we confirmed that the administration of an anti-IL-1α depleting antibody reduced metastasis. Conversely, the administration of recombinant IL-1α accelerated the lymphatic spreading of the tumor. Additionally, the elimination of the macrophages significantly reduced the progression of the metastatic spread. To understand the mechanism of action of IL-1α in the context of the lymph node microenvironment, we applied single-cell RNA sequencing to dissected metastases obtained from animals treated with an anti-IL-1α blocking antibody. Amongst the different pathways affected, we identified STAT3 as one of the main targets of IL-1α signaling in metastatic cells. Moreover, we found that the anti-IL-1α anti-tumoral effect was not mediated by lymphocytes, as IL-1R1 KO mice did not show any improvement in metastasis growth. Finally, we found a synergistic anti-metastatic effect of the combination of IL-1α blocking and the STAT3 inhibitor (STAT3i) stattic. In summary, we described a new mechanism by which SSM support melanoma metastasis, highlighting a new target for immunotherapy.

scholarly journals Peri-operative imaging techniques of the sentinel lymph node in veterinary oncology

2021 ◽  
Vol 90 (3) ◽  
pp. 115-124
Author(s):  
P. De Bie ◽  
S. Favril ◽  
S. De Vos ◽  
H. De Rooster
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Tumor Cells ◽  
Imaging Techniques ◽  
Lymphatic Vessels ◽  
Metastatic Tumor ◽  
Mapping Technique ◽  
Distant Metastatic Disease ◽  
Metastatic Cells ◽  
Lymphatic Pathway

When cancer cells spread through lymphatic vessels, the first lymph node they reach is the sentinel lymph node (SLN). Hence, if the SLN is free from metastatic cells, it can be assumed that further lymph nodes will be free of metastatic tumor cells too. If metastatic tumor cells are identified in the SLN, the patient is at risk of developing distant metastatic disease. In that case, further diagnostic and therapeutic steps are needed and the patient’s prognosis gets worse. The SLN can be located at an anatomically unpredictable location. This is likely due to lymphangiogenesis, which alters the normal lymphatic pathway and drains the metastatic cells to another lymph node than the expected anatomically closest one. Therefore, identifying the SLN by an accurate mapping technique is necessary. In this article, the existing techniques for SLN mapping are reviewed, and their use in human and veterinary medicine is compared.

scholarly journals Lymphangiogenesis and Its Correlation with the VEGF Expression and the Sentinel Lymph Node in Cutaneous Melanomas

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Petr Buzrla ◽  
Jana Dvorackova ◽  
Oldrich Motyka
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Stromal Cells ◽  
Lymphatic Vessels ◽  
Lymphatic Invasion ◽  
Sentinel Lymph Nodes ◽  
The Other ◽  
Melanoma Metastasis ◽  
Vegf Expression ◽  
The Status

The aim of the study is to evaluate the density of intratumoral and peritumoral lymphatic vessels in primary cutaneous melanomas and to assess their correlation with the status of sentinel lymph nodes and the VEGF expression in tumor cells and stromal cells. A total of 40 patients were enrolled in the study: the melanomas were radically excised with the extirpation of the sentinel lymph node. The study subjects were divided into two groups: 20 cases with positive and 20 cases with negative sentinel lymph node results. The density of lymphatic vessels was evaluated by the antibody D2-40 and the VEGF expression was investigated in the semiquantitative way. The VEGF expression in melanoma cells and the stromal cells was negative to variable positive at both SLN negative and SLN positive patients in all pT stages. In the group of SLN positive patients, the density of intratumoral lymphatic vessels was low up to moderate, while it was observed to be absent, somewhere on the low level in the group of SLN negative patients. On the other side, the density of peritumoral lymphatic vessels was equally numerous at both SLN negative and SLN positive patients. The lymphatic invasion was found out at 4 SLN positive patients only. The ulceration was chiefly in the group of LN positive patients. The results show that the density of lymphangiogenesis and the intensity of the VEGF expression are considered to be an unreliable predictor of melanoma metastasis to the sentinel lymph node, but the ulceration and the lymphatic invasion can predict the potential for metastasis.

Sentinel Lymph Node Chemokine Microenvironment Modulated by Melanoma Metastasis

2009 ◽  
pp. 227-235
Author(s):  
Minoru Kitago ◽  
Steve R. Martinez ◽  
Takuji Mori ◽  
Kazuo Koyanagi ◽  
Naoyuki Umetani ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Melanoma Metastasis

Conjunctival melanoma metastasis diagnosed by sentinel lymph node biopsy

2004 ◽  
Vol 137 (6) ◽  
pp. 1147-1149 ◽  
Author(s):  
Michael Baroody ◽  
John B Holds ◽  
Mimi S Kokoska ◽  
James Boyd
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Sentinel Lymph Node Biopsy ◽  
Lymph Node Biopsy ◽  
Melanoma Metastasis ◽  
Conjunctival Melanoma ◽  
Node Biopsy

Popliteal lymphadenectomy on sentinel lymph node melanoma metastasis

2006 ◽  
Vol 8 (3) ◽  
pp. 218-220 ◽  
Author(s):  
Antonio Barrasa Shaw ◽  
Francisca Sancho Merle ◽  
Carlos Fuster Diana ◽  
Jorge Campos Máñez ◽  
Carlos Vázquez Albadalejo
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Melanoma Metastasis

scholarly journals The pre-metastatic niche in lymph nodes: formation and characteristics

2021 ◽  
Author(s):  
Lionel Gillot ◽  
Louis Baudin ◽  
Loïc Rouaud ◽  
Frédéric Kridelka ◽  
Agnès Noël
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Current Knowledge ◽  
Lymphatic Vessels ◽  
Matrix Composition ◽  
Matrix Remodeling ◽  
Metastatic Niche ◽  
Future Directions ◽  
Metastatic Cells ◽  
Immunosuppressive Cell

AbstractLymph node metastasis is a crucial prognostic parameter in many different types of cancers and a gateway for further dissemination to distant organs. Prior to metastatic dissemination, the primary tumor prepares for the remodeling of the draining (sentinel) lymph node by secreting soluble factors or releasing extracellular vesicles that are transported by lymphatic vessels. These important changes occur before the appearance of the first metastatic cell and create what is known as a pre-metastatic niche giving rise to the subsequent survival and growth of metastatic cells. In this review, the lymph node structure, matrix composition and the emerging heterogeneity of cells forming it are described. Current knowledge of the major cellular and molecular processes associated with nodal pre-metastatic niche formation, including lymphangiogenesis, extracellular matrix remodeling, and immunosuppressive cell enlisting in lymph nodes are additionally summarized. Finally, future directions that research could possibly take and the clinical impact are discussed.

scholarly journals The lymphatic system and sentinel lymph nodes: conduit for cancer metastasis

2021 ◽  
Author(s):  
Stanley P. Leong ◽  
Alexander Pissas ◽  
Muriel Scarato ◽  
Francoise Gallon ◽  
Marie Helene Pissas ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Lymph Nodes ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Early Cancer ◽  
Lymphatic Vessels ◽  
Review Article ◽  
Cancer Spread

AbstractThe lymphatic system is a complicated system consisting of the lymphatic vessels and lymph nodes draining the extracellular fluid containing cellular debris, excess water and toxins to the circulatory system. The lymph nodes serve as a filter, thus, when the lymph fluid returns to the heart, it is completely sterile. In addition, the lymphatic system includes the mucosa-associated lymphoid tissue, such as tonsils, adenoids, Peyers patches in the small bowel and even the appendix. Taking advantage of the drainage system of the lymphatics, cancer cells enter the lymphatic vessels and then the lymph nodes. In general, the lymph nodes may serve as a gateway in the majority of cases in early cancer. Occasionally, the cancer cells may enter the blood vessels. This review article emphasizes the structural integrity of the lymphatic system through which cancer cells may spread. Using melanoma and breast cancer sentinel lymph node model systems, the spread of early cancer through the lymphatic system is progressive in a majority of cases. The lymphatic systems of the internal organs are much more complicated and difficult to study. Knowledge from melanoma and breast cancer spread to the sentinel lymph node may establish the basic principles of cancer metastasis. The goal of this review article is to emphasize the complexity of the lymphatic system. To date, the molecular mechanisms of cancer spread from the cancer microenvironment to the sentinel lymph node and distant sites are still poorly understood and their elucidation should take major priority in cancer metastasis research.

scholarly journals Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

2020 ◽  
pp. 319-334 ◽  
Author(s):  
Domenico Bellomo ◽  
Suzette M. Arias-Mejias ◽  
Chandru Ramana ◽  
Joel B. Heim ◽  
Enrica Quattrocchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Nodal Metastasis ◽  
Low Risk ◽  
Tissue Type ◽  
Next Generation Sequencing Data ◽  
Melanoma Metastasis ◽  
Mesenchymal Transition ◽  
Biopsy Procedure

PURPOSE More than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here, we describe a model that combines clinicopathologic and molecular variables to identify patients with thin- and intermediate-thickness melanomas who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis. PATIENTS AND METHODS Genes with functional roles in melanoma metastasis were discovered by analysis of next-generation sequencing data and case-control studies. We then used polymerase chain reaction to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin- and intermediate-thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross-validation scheme to predict the presence of SLN metastasis from molecular, clinical, and histologic variables. RESULTS Expression of genes with roles in epithelial-to-mesenchymal transition (glia-derived nexin, growth differentiation factor 15, integrin-β3, interleukin 8, lysyl oxidase homolog 4, transforming growth factor-β receptor type 1, and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model that included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age (area under the receiver operating characteristic curve, 0.82; 95% CI, 0.78 to 0.86; SLN biopsy reduction rate, 42%; negative predictive value, 96%). CONCLUSION A combined model that included clinicopathologic and gene expression variables improved the identification of patients with melanoma who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.

scholarly journals Lymph-Derived Neutrophils Primarily Locate to the Subcapsular and Medullary Sinuses in Resting and Inflamed Lymph Nodes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1486
Author(s):  
Jenny de Castro de Castro Pinho ◽  
Reinhold Förster
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Tissue Injury ◽  
Lymphatic Vessels ◽  
Functional Behavior ◽  
Subcapsular Sinus ◽  
Activated Neutrophils ◽  
Tissue Site

Neutrophils are the first immune cells to be recruited from the blood to the tissue site of an infection or inflammation. It has been suggested that neutrophils are capable of migrating from the infected tissue via lymphatic vessels to the draining lymph nodes. However, it remains elusive as to which areas within the lymph nodes can be reached by such reversely migrating cells. To address this question, we applied a model for adoptive neutrophil transfer into the afferent lymphatic vessel that drains towards the popliteal lymph node in mice. We showed that resting and in vitro-activated neutrophils did not enter the lymph node parenchyma but localized primarily in the subcapsular and medullary sinuses. Within the medulla, neutrophils show random migration and are able to sense laser-induced sterile tissue injury by massively swarming to the damaged tissue site. Co-injected dendritic cells supported the entry of resting neutrophils into the lymph node parenchyma via the subcapsular sinus. In contrast, in vivo-activated adoptively transferred neutrophils were capable of migrating into the interfollicular areas of the lymph node. Collectively, the data presented here give further insights into the functional behavior of neutrophils within the lymph nodes.

scholarly journals Metastatic Merkel cell carcinoma and malignant melanoma in a single sentinel lymph node

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110236
Author(s):  
Amanda Hamilton ◽  
Prasad Jayaratne ◽  
Mark Zonta
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Malignant Melanoma ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Lymph Node Biopsy ◽  
The Body ◽  
Ageing Population ◽  
Merkel Cell ◽  
Dual Diagnoses

Merkel cell carcinoma (MCC) and malignant melanoma are aggressive skin cancers that usually arise in sun-exposed parts of the body. This report describes an 85-year-old man who underwent a wide local excision and sentinel lymph node biopsy for primary MCC and was subsequently found to have metastatic MCC and malignant melanoma within the left inguinal sentinel lymph node. Dual diagnoses of aggressive cutaneous carcinomas, although rare, may become more common in regions of high ultraviolet exposure and an ageing population. Currently, there are no guidelines for treating synchronous MCC and melanoma, however, immunotherapy with PD-1 inhibitors and anti-CTLA-4 receptor antagonists have shown therapeutic effect against these two cancers and should be considered in treatment planning.

Sign in / Sign up

Export Citation Format

Share Document