The lymph node microenvironment and its role in the progression of metastatic cancer

Pereira, Ethel R.; Jones, Dennis; Jung, Keehoon; Padera, Timothy P.

doi:10.1016/j.semcdb.2015.01.008

Cited by 146 publications

(137 citation statements)

References 109 publications

(121 reference statements)

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“…acute myeloid leukemia; AML) and is likely the case for solid tumor cancer cells as well. The microenvironments that comprise various tumor niches are very divergent and depend on the particular cancer (2)(3)(4)(5)(6). The cancer cells which pose the greatest danger to the patient and traditionally are the hardest to eliminate are the cancer stem cells (CSC, or LSC for leukemia stem cells; reviewed in refs 7-11).…”

Section: Introductionmentioning

confidence: 99%

Galectin 3 as a guardian of the tumor microenvironment

Ruvolo

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

167

159

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Galectin 3 is a member of a family of β-galactoside binding proteins and has emerged as an important regulator of diverse functions critical in cancer biology including apoptosis, metastasis, immune surveillance, molecular trafficking, mRNA splicing, gene expression, and inflammation. Galectin 3's ability to support cancer cell survival by intra-cellular and extra-cellular mechanisms suggests this molecule is an important component of the tumor microenvironment that potentially could be targeted for therapy. Data is emerging that Galectin 3 is elevated in many cancers including solid tumors and the cancers of the blood. Galectin 3 also appears to be a key molecule produced by tumor microenvironment support cells including mesenchymal stromal cells (MSC) to suppress immune surveillance by killing T cells and interfering with NK cell function and by supporting metastasis. Levels of Galectin 3 increase in the MSC of aging mice and perhaps this contributes to the development of cancer in the elderly. Galectin 3 modulates surface protein expression of a diverse set of glycoproteins including CD44 by regulating endocytosis of these proteins. In addition, Galectin 3 binding to receptor kinases such as CD45 and the T cell receptor is critical in the regulation of their function. In this review I will examine the various mechanisms how Galectin 3 supports chemoresistance and metastasis in solid tumors and in leukemia and lymphoma. I will also discuss possible therapeutic strategies to target this Galectin for cancer therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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Section: Introductionmentioning

confidence: 99%

Galectin 3 as a guardian of the tumor microenvironment

Ruvolo

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

167

159

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“…7,38,39 In the present study, we identified the novel CD169 C CD8 C T cells, which were selectively concentrated in the LN tissues from both cancer patients and control donors, but rarely found in the primary tumors, peripheral blood, or control tonsils. CD169 C CD8 C T cells are effector memory cells that have a highly activated and cytolytic phenotype, and their levels were decreased in the paracolic LN close to the primary tumor.…”

Section: Discussionmentioning

confidence: 66%

“…Additionally, tumors have been suggested to significantly modulate the microenvironment of LNs. 37,38,40 Thus, a better understanding of the mechanism of tumor-modulating CD169 C CD8 C T cells may be used to develop new cancer immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

CD169 identifies an activated CD8⁺T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

Zhang

et al. 2016

OncoImmunology

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Purpose: CD169 was first identified on macrophages (Mf) and linked to antigen presentation. Here, we showed CD169 expression on some CD8 C T lymphocytes in regional lymph nodes (LNs) and investigated the function and clinical relevance of CD169 C CD8 C T cells in tumor-draining LNs of colorectal cancer (CRC) patients. Experimental design: Fresh tumor-draining LN tissues from 39 randomly enrolled patients were assessed by flow cytometry for activation and differentiation of CD169 C CD8 C T cells and T cell-mediated killing of tumor cells. In total, 114 tumor-draining LN paraffin sections from CRC patients were analyzed by multiplecolor immunofluorescence for CD169 C CD8 C T cell distribution and clinical values. The prognostic significance of CD169 C CD8 C T cells was evaluated by Kaplan-Meier analysis. Results: A fraction of CD8 C T cells in regional LNs, but not peripheral blood, tonsils, or tumors, expressed surface CD169. In situ detection of draining LNs revealed preferential localization of CD169 C CD8 C T cells to subcapsular sinus and interfollicular regions, closely associated with CD169 C Mf. CD169 C CD8 C T cell ratios were significantly lower in peri-tumor LNs than distant-tumor LNs. CD169 C CD8 C T cells predominantly expressed activation markers (CD69, HLA-DR, PD-1) with slightly lower CD45RA and CD62L levels. They produced high granzyme B, perforin, TNF-a, and IFNg levels, and promoted tumor-killing efficiency ex vitro. Moreover, CD169 C CD8 C T cells infiltrating tumor-draining LNs decreased with disease progression and were strongly associated with CRC patient survival. Conclusions: We identified novel activated/cytolytic CD169 C CD8 C T cells selectively present in regional LNs, potentially serving as a powerful prognostic factor and indicator for selecting patients for immunotherapy.

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“…6 Chemoradiation or elective neck dissection (END) should be considered in patients 7 The microenvironment of the lymph node is initially hostile to cancer cells due to a predominance of immune effector cells and cytokines; immunoresistant clones in the hostile lymph node milieu subsequently proliferate, spread and invade the rest of the lymphatic system to establish metastasis. 8 Malignant cells follow an orderly sequence, spreading from one nodal basin to the next as the disease progresses down the neck. In some situations, lymph node groups can be bypassed, which can result in a process known as skip metastasis.…”

Section: Nodal Metastasis N O D a L M E Ta S Tat I C C A S C A D Ementioning

confidence: 99%

Sentinel Lymph Node Biopsy: A new approach in the management of head and neck cancers

Sharma¹,

Koshy²,

Grover³

et al. 2017

SQUMJ

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‫شارما‬ ‫بوشان‬ ‫جروفر,‬ ‫سونال‬ ‫كوشي,‬ ‫جورج‬ ‫شارما,‬ ‫ديبيت‬ abstract: Cervical lymph node metastasis affects the prognosis and overall survival rate of and therapeutic planning for patients with head and neck squamous cell carcinomas (HNSCCs). However, advanced diagnostic modalities still lack accuracy in detecting occult neck metastasis. A sentinel lymph node biopsy is a minimally invasive auxiliary method for assessing the presence of occult metastatic disease in a patient with a clinically negative neck. This technique increases the specificity of neck dissection and thus reduces morbidity among oral cancer patients. The removal of sentinel nodes and dissection of the levels between the primary tumour and the sentinel node or the irradiation of target nodal basins is favoured as a selective treatment approach; this technique has the potential to become the new standard of care for patients with HNSCCs. This article presents an update on clinical applications and novel developments in this field. A s opposed to primary tumours, metastasis is responsible for the high mortality rate of most cancer patients; moreover, cancer cells primarily invade the regional lymph nodes before spreading to other parts of the body. Keywords1 Genetic instability results in tumour cell heterogeneity, leading to the emergence of metastatic clones and dissemination of the cancer from the primary tumour site.2 Malignant cells metastasise due to an interaction between the host factors and tumour cells. Genes related to the extracellular matrix, adhesion, motility and protease inhibition constitute a significant part of the metastatic process. The migration and invasion of cancer cells into the lymphatic system is governed by a variety of intricate genotypic, phenotypic and microenvironmental processes. After entering the lymphatic draining channels, the tumour cells metastasise to the regional lymph nodes in the neck and form the metastatic foci.4 Macrometastases refer to lymph nodes that appear suspicious on clinical or radiographical examinations; in contrast, nodal metastases-which are not detectable by imaging methods or physical examination-indicate occult or subclinical metastasis. Hermanek microscopically differentiated occult metastases into macrometastases (metastatic deposits of >2 mm), micrometastases (metastatic deposits of <2 mm) and isolated or small clusters of tumour cells (metastatic deposits of <0.2 mm).5 Isolated tumour cells (ITCs) can also be defined as a cluster of ≤200 tumour cells visible on one histology slide; these cells can further be categorised into those detectable by light microscopy, immunohistochemistry or molecular methods.6 Chemoradiation or elective neck dissection (END) should be considered in patients

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The lymph node microenvironment and its role in the progression of metastatic cancer

Cited by 146 publications

References 109 publications

Galectin 3 as a guardian of the tumor microenvironment

Galectin 3 as a guardian of the tumor microenvironment

CD169 identifies an activated CD8⁺T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

Sentinel Lymph Node Biopsy: A new approach in the management of head and neck cancers

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The lymph node microenvironment and its role in the progression of metastatic cancer

Cited by 146 publications

References 109 publications

Galectin 3 as a guardian of the tumor microenvironment

Galectin 3 as a guardian of the tumor microenvironment

CD169 identifies an activated CD8+T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

Sentinel Lymph Node Biopsy: A new approach in the management of head and neck cancers

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CD169 identifies an activated CD8⁺T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients