Histopathology of Immunologic Regression of Tumor Metastasis in the Lymph Nodes

Kodama, Takao; Gotohda, Eiki; Takeichi, Noritoshi; Kuzumaki, Noboru; Kobayashi, Hiroshi

doi:10.1093/jnci/52.3.931

Cited by 17 publications

(9 citation statements)

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“…The following phase was characterized by inundation of tumor cells via the marginal sinuses and formation of colonies, with completion of the process of metastasis by 7 days after inoculation. The finding that the marginal sinus is the initial site of cancer cell proliferation in the regional lymph node is consistent with previous reports (4,5,9,10,25). Proliferation of cancer 4 days after inoculation is probably due to clonal expansion of cancer cells that are resistant to the host defense.…”

Section: Discussionsupporting

confidence: 92%

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Limited Capability of Regional Lymph Nodes to Eradicate Metastatic Cancer Cells

et al. 2004

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The capacity of lymph nodes to eradicate cancer is a controversial issue. The purpose of this study was to determine the interplay between tumor growth and host resistance at early stages of lymph node metastasis. A metastasis model was made in the rat mesenteric lymph node, and migration of cancer cells was visualized in vivo. The lymph node was removed for histologic analysis and cytokine measurement. Migrant cancer cells were initially arrested in the marginal sinus. After an initial increase, the number of cancer cells in the marginal sinus declined until 48 hours after inoculation. Germinal centers and lymphoid cells in the medulla proliferated before 48 hours. ED3؉ macrophages incorporated apoptotic cancer cells, but significant cancer proliferation occurred after 4 days. Lymph nodes depleted of macrophages were massively invaded by cancer cells. Tumor necrosis factor ␣ and interleukin (IL)-1␤ in the nodes transiently increased after 1 hour and 3 hours, respectively, and were expressed in ED3 ؉ and ED2 ؉ macrophages, respectively. These changes were followed by a transient increase in IL-2. Interferon-␥ and IL-12 did not increase during the early stages of metastasis, but they decreased after 48 hours. In conclusion, the marginal sinus constitutes a mechanical barrier against cancer cell passage. Early pathological manifestations in the regional lymph node are consistent with those in cancer patients with improved survival. Parasinus macrophages play a role in the transient antimetastatic capability of the node, and cytokines secreted by these cells increased at the early stages of metastasis. Deterioration of cytokine induction may be responsible for subsequent cancer proliferation.

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Section: Discussionsupporting

confidence: 92%

“…A small number of tumor cells seem to be rejected in the regional lymph node in situ (9,10). Clearly, the biological responses of lymph nodes during the process of metastasis are based on their immune responses (9 -11).…”

Section: Introductionmentioning

confidence: 99%

Limited Capability of Regional Lymph Nodes to Eradicate Metastatic Cancer Cells

et al. 2004

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“…There is however one remarkable series of experiments (50) in which regression occured after infection of the tumor cells with virus. When 5 million uninfected tumor cells were injected into the footpad, there was consistent metastasis to popliteal lymph nodes, thence further up the lymphatic chain, killing the rats in about 18 days.…”

Section: Lymphatic Metastasismentioning

confidence: 99%

“…In one model in which there was concomitant viral infection, this certainly occurred (50); and there is inferential evidence that it can occur during chemotherapy. It may be possible even in the absence of therapy (58,59).…”

Section: Lymphatic Metastasismentioning

confidence: 99%

Lymphatic metastasis

Carr

1983

Cancer Metast Rev

114

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Lymphatic metastasis is an important mechanism in the spread of human cancer. During its course, tumor cells first penetrate the basement of membrane of the epithelium, in which they arise, and then the underlying connective tissue, carried partly by hydrostatic pressure. They enter the lymphatic partly by active movement, pass up the lymphatic trunk; they then settle and proliferate in the subcapsular sinus, penetrate its endothelium and proliferate and destroy the node. There are varied forms of immune response in the node and in human nodes often a complex fibrous and vascular response. The degree of lymphocytic response may be important for prognosis. The nodal reaction may be stimulated by release of antigens from the tumor. One of the most studied animal models of lymphatic metastasis is that which occurs in the politeal node after injection of tumor into the footpad. This model has been used to show that tumor cells enter lymphatics through gaps in endothelium, probably between endothelial cells, and that lymph nodes can destroy small numbers of tumor cells. Local immunotherapy and chemotherapy can sterilize a lymph node of tumor cells; the modes of treatment used have included intralymphatic injection and encapsulation of chemotherapeutic agents in liposomes. Prior radiotherapy may accelerate metastasis possibly by making tumor cells shed into lymphatic vessels. Lymph nodes are rather poor barriers to tumor cells. The prognostic significance of lymph node metastasis varies within tumor type; if hematogenous metastasis is early, then the presence of lymph node metastasis is of lesser prognostic significance. Lymph nodes can probably destroy only small numbers of tumor cells. Tumor cell heterogeneity is of importance in many aspects of metastasis; while clonal variation may be of importance in determining lymph node metastasis, it is not yet clear how important this is, nor whether specific clones metastasize specifically to lymph nodes. Lymphography is well established in diagnosis of lymphatic metastasis. A recent interesting development has been to inject antibodies labeled with a radioactive label, and image the label in lymph nodes with a gamma-camera. If anti-tumor antibodies are used in this way it may be possible to detect lymph node metastasis. Within the expanding field of tumor metastasis, lymphatic metastasis needs much more attention, particularly in relation to the diagnosis and treatment of the lymphatic spread of human cancer.

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“…Известно, что характер метастазирования зависит от им-мунного статуса регионарного лимфатического узла. Показана регрессия метастазов в регионарных лимфати-ческих узлах при лимфосаркоме WGT-4 на 10 день после инъекции опухолевых клеток в ткань бедра нормальных крыс и гибель животных в результате мощного опухоле-вого роста и метастазирования у иммуносупрессивных животных [13]. При изучении зависимости показателей иммуно-функци-онального состояния регионарного лимфатического кол-лектора от возраста больных установлено, что в группе пациентов старше 60 лет отмечается снижение общего количества лимфоидных клеток в лимфатическом узле, что свидетельствует о снижении регионарного противоо-пухолевого барьера [14].…”

Section: обзор представленного материалаunclassified

The Biological Conceptualization of the Sentinel Lymph Node (Literature Review)

Ермаков¹,

Зикиряходжаев²,

Сарибекян³

et al. 2016

Zlokač. opuholi

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ВВЕДЕНИЕОперация лимфаденэктомия, как важный этап диагности-ки и противоопухолевого лечения, сопровождается значи-тельным риском развития осложнений, в частности лим-фэдемы, потери чувствительности определенных участков кожи и худшего заживления ран. Эта операция, также, приводит к возрастанию финансовых затрат на лечение больных вследствие большей продолжительности анесте-зии, более длительного пребывания в операционной и за-

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Histopathology of Immunologic Regression of Tumor Metastasis in the Lymph Nodes

Cited by 17 publications

References 0 publications

Limited Capability of Regional Lymph Nodes to Eradicate Metastatic Cancer Cells

Limited Capability of Regional Lymph Nodes to Eradicate Metastatic Cancer Cells

Lymphatic metastasis

The Biological Conceptualization of the Sentinel Lymph Node (Literature Review)

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