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Lymphatics, Volume 3, Issue 2 (June 2025) – 5 articles

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16 pages, 10251 KiB  
Article
Specific Position of the Pulmonary Hilar Node in Cancer Immunity: Immunohistochemical and Morphometrical Study Using Lung Regional Nodes Obtained from Non-Small Cell Cancer Patients Without Metastasis
by Masaya Aoki, Go Kamimura, Aya Harada-Takeda, Toshiyuki Nagata, Gen Murakami and Kazuhiro Ueda
Lymphatics 2025, 3(2), 13; https://doi.org/10.3390/lymphatics3020013 - 21 May 2025
Abstract
Background: Nodal dendritic cells (DCs) and CD169-positive macrophages, possibly monocyte-derived, cross-present cancer antigens earlier in the proximal node than in the distal node. Methods: We performed immunohistochemical and morphometric analyses to show differences in the distributions of DC-SIGN-, CD68-, and CD169-positive cells in [...] Read more.
Background: Nodal dendritic cells (DCs) and CD169-positive macrophages, possibly monocyte-derived, cross-present cancer antigens earlier in the proximal node than in the distal node. Methods: We performed immunohistochemical and morphometric analyses to show differences in the distributions of DC-SIGN-, CD68-, and CD169-positive cells in the paratracheal, subcarinal, and hilar nodes from 25 non-small cell lung cancer patients without metastasis. Results: CD169-positive and DC-SIGN-positive cells were colocalized in the subcapsular and paracortical sinuses, whereas CD68-positive, self-renewal alveolar macrophages were present in the medullary sinus. This complementary distribution was more evident in nodes other than hilar nodes. In hilar nodes, the proportion of CD68-positive macrophages usually exceeds 50%. Notably, the proportion of the overlapped cluster between CD169-positive cells and DC-SIGN-positive cells, which likely corresponds to the cross-presentation activity, was almost the same between the hilar and “next-upstream” node (i.e., the paratracheal node for the upper lobe and the subcarinal node for the lower lobe). Monocyte-derived cells occupied a significantly larger area in the hilar nodes of patients with upper lobe cancer than in patients with lower lobe cancer (p = 0.002–0.009). Conclusion: The specific site occupying the lung hilum with collateral vessels seemed to determine the hilar node composite cells. Full article
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22 pages, 759 KiB  
Review
From Mechanisms to Treatment: A Comprehensive View of Lymphatic Metastasis in Cancer
by Nitya Devisetti, Pushti Shah and Farrah C. Liu
Lymphatics 2025, 3(2), 12; https://doi.org/10.3390/lymphatics3020012 - 19 May 2025
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Abstract
The lymphatic system, a complex and dynamic network comprising lymphatic vessels, lymph nodes (LNs), and associated lymphoid tissues, plays a pivotal role in regulating interstitial fluid balance and providing immune surveillance across the body. In cancer, however, the lymphatic system often transforms into [...] Read more.
The lymphatic system, a complex and dynamic network comprising lymphatic vessels, lymph nodes (LNs), and associated lymphoid tissues, plays a pivotal role in regulating interstitial fluid balance and providing immune surveillance across the body. In cancer, however, the lymphatic system often transforms into a pathway for malignant cell dissemination, leading to lymphatic metastasis—a significant step in tumor progression associated with worse patient prognoses. Mechanistically, tumor cells exploit lymphangiogenic pathways to facilitate their entry and spread within the lymphatic network. Key mechanisms in this process include the upregulation of vascular endothelial growth factors C and D (VEGF-C/D), which promote lymphatic endothelial proliferation, vessel dilation, and increased permeability. This review seeks to provide an in-depth examination of the biological mechanisms underpinning lymphatic metastasis, explore its impact on cancer progression, and highlight current and emerging strategies aimed at managing metastatic disease. Full article
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12 pages, 549 KiB  
Article
Lipoperoxides as Prognostic Markers in Pediatric B-Acute Lymphocytic Leukemia Patients Undergoing Induction Chemotherapy
by Bruna Yukie Koizumi, Marina Rayciki Sotomayor, Carolina Coradi, Ana Luiza Goulart Starck, Anna Will Ribeiro, Maikely Bruna Leite, Maria Eduarda Pardal Simonato, Rafael Gomes Paz, Vinicius de Melo Tizzo, Stefania Tagliari Longo, Geise Ellen Broto, Fausto Celso Trigo and Carolina Panis
Lymphatics 2025, 3(2), 11; https://doi.org/10.3390/lymphatics3020011 - 19 May 2025
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Abstract
B-type acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Despite significant advancements in treatment, chemotherapy resistance and relapse remain major challenges to be overcome. Oxidative stress markers, including lipoperoxides, have emerged as potential biomarkers in B-ALL patients under treatment. This study [...] Read more.
B-type acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Despite significant advancements in treatment, chemotherapy resistance and relapse remain major challenges to be overcome. Oxidative stress markers, including lipoperoxides, have emerged as potential biomarkers in B-ALL patients under treatment. This study evaluated lipoperoxide levels in the peripheral blood of pediatric B-ALL patients during the induction phase of chemotherapy using high-sensitivity chemiluminescence and analyzed their association with clinical prognostic factors and patient outcomes, including definitive hospital discharge, disease relapse, and patient death. Lower lipoperoxide levels were observed in patients over 10 years old, those who achieved remission and were discharged from the hospital, and those with central nervous system (CNS) involvement. In contrast, significantly higher lipoperoxide levels were found in patients who relapsed, died, or had platelet counts exceeding 50,000/mm3. Receiver operating characteristic (ROC) curve analysis suggests that lipoperoxides may serve as potential biomarkers during the induction phase of chemotherapy, distinguishing B-ALL patients undergoing treatment from those not in treatment (sensitivity: 92.31%; specificity: 71.43%). These findings highlight the potential utility of lipoperoxides as prognostic biomarkers in B-ALL patients. Full article
(This article belongs to the Collection Acute Lymphoblastic Leukemia (ALL))
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15 pages, 2994 KiB  
Review
Immunoglobulin-Related Fibroinflammatory Diseases of Uncertain Etiology—Polarized Isotype Switching Connects an Ancient with a Contemporary Disease
by Chi Sing Ng
Lymphatics 2025, 3(2), 10; https://doi.org/10.3390/lymphatics3020010 - 15 Apr 2025
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Abstract
IgG4 is an unusual immunoglobulin (Ig) and is the least component of IgG in humans. It is often asymmetrical and heterobivalent with weak Fc (fragment crystallizable region)-dependent effector function and ineffective complement activation, thus playing an unclear role in immune functions. IgE is [...] Read more.
IgG4 is an unusual immunoglobulin (Ig) and is the least component of IgG in humans. It is often asymmetrical and heterobivalent with weak Fc (fragment crystallizable region)-dependent effector function and ineffective complement activation, thus playing an unclear role in immune functions. IgE is an uncommon Ig, being important mostly in allergy and type 2 immunity. There are two rare chronic Ig-related fibroinflammatory diseases, namely IgG4-related disease (IgG4RD) and Kimura disease (KD), characterized by prominent IgG4- or IgE-positive plasma cells in the affected tissues, with or without blood elevations of the same Ig. The etiology of these two Ig-related diseases is unclear, though it appears that the pathogenesis in both is related to polarized Ig heavy chain isotype switching, concomitant with other cellular, cytokine and chemotaxin interactions that culminates in the characteristic pathologic manifestations of inflammation and fibrosis. IgG4RD and KD, despite having overlapping and differing features, may be connected by the similar pathogenetic polarized Ig isotype switching. Full article
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24 pages, 4752 KiB  
Review
New Facets of Hematolymphoid Eponymic Diseases
by Chi Sing Ng and Jilong Qin
Lymphatics 2025, 3(2), 9; https://doi.org/10.3390/lymphatics3020009 - 9 Apr 2025
Viewed by 207
Abstract
Disease eponyms can be confusing, difficult to remember, scientifically non-robust, and lacking in implications on and relationships with cell lineage, histogenesis, and pathogenesis. This review is geared toward revisiting hematolymphoid diseases with eponyms in light of recent advances in technology and science by [...] Read more.
Disease eponyms can be confusing, difficult to remember, scientifically non-robust, and lacking in implications on and relationships with cell lineage, histogenesis, and pathogenesis. This review is geared toward revisiting hematolymphoid diseases with eponyms in light of recent advances in technology and science by searching the past fifty years of the literature using Scopus and Google Scholar with the keywords “eponyms, hematolymphoid, diseases, lymphoma, benign, malignant, lymph node, spleen, liver, bone marrow, leukemia”. With advances in science and technology, there is accumulation of information on the morphologic nuances and immunologic, immunophenotypic, and genetic features of various hematolymphoid eponymic diseases, thus shedding light on important issues of etiology and pathogenesis with implications on therapy in various non-neoplastic (Castleman, Evans syndrome Kikuchi–Fujimoto, IgG4-related diseases) and neoplastic (Hodgkin, Burkitt, NK/T-cell lymphomas, dendritic/histiocytic neoplasms, and Sezary syndrome) diseases. This contributes to modern nomenclature, classification, subtyping, prognostication, and discoveries on new treatment strategies of hematolymphoid eponymic diseases. Full article
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