Lymphoproliferative responses and protection in conventional piglets inoculated orally with virulent or attenuated porcine epidemic diarrhoea virus

Lymphocyte proliferative responses were evaluated in mucosal (mesenteric lymph nodes) and systemic (spleen and blood) lymphoid tissues of conventional piglets inoculated with the virulent or attenuated isolates of porcine epidemic diarrhoea virus (PEDV) strain CV-777 and challenged 21 days later with the virulent isolate of the same virus. A lymphoproliferative assay was developed in which mononuclear cells isolated from lymphoid tissues at different postinoculation and postchallenge days underwent a secondary in vitro stimulation with semipurified antigen obtained from PEDV-infected cell cultures. Vigorous lymphocyte proliferative responses were detected in the pigs inoculated with the virulent PEDV at postinoculation days 4-21, especially in the mesenteric lymph nodes and the blood; however, in the spleen this response was lower and less regular. The pigs inoculated with the attenuated virus showed a less intense response, the higher lymphocyte proliferation also corresponded to the mononuclear cells from mesenteric lymph nodes. Lymphocyte proliferation responses showed high correlations with protection against homologous challenge with virulent PEDV, and this correlation was higher in the gut associated lymphoid tissues (mesenteric lymph nodes). The cell proliferation response detected in blood mirrored that detected in the mesenteric lymph nodes, and showed also good correlation with protection. The results confirm that T-cell-helper function, assessed by lymphocyte proliferation responses, contributes to establishing a protective immune response against PEDV infections.     

Detection of Immune Responses in Sentinel Nodes Draining Human Urinary Bladder Cancer

Being the first lymph node to receive drainage from the tumour area, the sentinel node offers a unique possibility to obtain tumour-reactive lymphocytes. We investigated antitumour immune responses in sentinel nodes from patients with bladder cancer, by assaying tumour-specific proliferation and TCR Vβ repertoires. During tumour surgery, sentinel lymph nodes were identified by peri-tumoural injection of blue dye. Fresh specimens of tumour, sentinel and nonsentinel lymph nodes were obtained, and single-cell suspensions were prepared. Cells were assayed for reactivity against autologous tumour extract in [³H]-thymidine incorporation assays and characterized by flow cytometry. Parallel analyses of the expression of Vβ gene families were performed with padlock probes, linear oligonucleotides which upon target recognition can be converted to circular molecules by a ligase. Probes were reacted with cDNA prepared from magnetically separated CD4⁺ cells, and the TCR repertoire was determined by hybridizing the products to oligonucleotide microarrays. Dose-dependent proliferation in response to tumour extract could be detected in sentinel lymph nodes. Common clonal expansions were detected among tumour-infiltrating lymphocytes and in sentinel lymph nodes. Nonsentinel lymph nodes displayed a divergent TCR Vβ repertoire. These results indicate an ongoing immune response against tumour antigens in sentinel nodes, draining urinary bladder cancer. Identification of sentinel lymph nodes makes it possible to obtain tumour-reactive lymphocytes for use in adoptive immunotherapy.     

LYMPH NODE INVOLVEMENT IN WALDENSTROM'S MACROGLOBULINEMIA

The pattern of lymph node involvement in Waldenström's macroglöbulinemia (MG) is described according to clinical and histological materials from 2 biopsy and 4 autopsy cases. The histological features of biopsy were well-differentiated, diffuse, lymphocytic lymphoma in one case (case 1) and sinus histiocytosis (SH) with nodular aggregates of lymphoid cells as observed by the first biopsy in the other case (case 2). An immunofluorescent study of lymph nodes revealed monoclonal proliferation of B lymphocytes (IgM, κ) in both cases. In case 2, a majority of circulating lymphoid cells bore membrane-bound monoclonal IgM. The histological features of lymph nodes obtained by the second biopsy in case 2 was comparable with the well-differentiated, lymphocytic lymphoma in some nodes, and diffuse and nodular proliferation with preservation of sinuses in the other nodes. The pattern of lymph node involvement of 4 autopsy cases were also analysed. According to these investigations, It is suggested that lymph node showing SH is a pattern of lymph node involvement of MG.     

Lymph node involvement in Waldenstr?m's macroglobulinemia

The pattern of lymph node involvement in Waldenstr?m's macr?globulinemia (MG) is described according to clinical and histological materials from 2 biopsy and 4 autopsy cases. The histological features of biopsy were well-differentiated, diffuse, lymphocytic lymphoma in one case (case 1) and sinus histiocytosis (SH) with nodular aggregates of lymphoid cells as observed by the first biopsy in the other case (case 2). An immunofluorescent study of lymph nodes revealed monoclonal proliferation of B lymphocytes (IgM, gamma) in both cases. In case 2, a majority of circulating lymphoid cells bore membrane-bound monoclonal IgM. The histological features of lymph nodes obtained by the second biopsy in case 2 was comparable with the well-differentiated, lymphocytic lymphoma in some nodes, and diffuse and nodular proliferation with preservation of sinuses in the other nodes. The pattern of lymph node involvement of 4 autopsy cases were also analysed. According to these investigations. It is suggested that lymph node showing SH is a pattern of lymph node involvement of MG.     

Surgical excision of CNS‐draining lymph nodes reduces relapse severity in chronic‐relapsing experimental autoimmune encephalomyelitis

Despite lack of classical lymphatic vessels in the central nervous system (CNS), cells and antigens do reach the CNS‐draining lymph nodes. These lymph nodes are specialized to mediate mucosal immune tolerance, but can also generate T‐ and B‐cell immunity. Their role in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) therefore remains elusive. We hypothesized that drainage of CNS antigens to the CNS‐draining lymph nodes is vital for the recurrent episodes of CNS inflammation. To test this, we surgically removed the superficial cervical lymph nodes, deep cervical lymph nodes, and the lumbar lymph nodes prior to disease induction in three mouse EAE models, representing acute, chronic, and chronic‐relapsing EAE. Excision of the CNS‐draining lymph nodes in chronic‐relapsing EAE reduced and delayed the relapse burden and EAE pathology within the spinal cord, which suggests initiation of CNS antigen‐specific immune responses within the CNS‐draining lymph nodes. Indeed, superficial cervical lymph nodes from EAE‐affected mice demonstrated proliferation against the immunizing peptide, and the deep cervical lymph nodes, lumbar lymph nodes, and spleen demonstrated additional proliferation against other myelin antigen epitopes. This indicates that intermolecular epitope spreading occurs and that CNS antigen‐specific immune responses are differentially generated within the different CNS‐draining lymphoid organs. Proliferation of splenocytes from lymphadenectomized and sham‐operated mice against the immunizing peptide was similar. These data suggest a role for CNS‐draining lymph nodes in the induction of detrimental immune responses in EAE relapses, and conclusively demonstrate that the tolerance‐inducing capability of cervical lymph nodes is not involved in EAE. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Interval sentinel lymph nodes in melanoma: a digital pathology analysis of Ki67 expression and microvascular density

The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest that the correlation between tumor cell proliferation and neo-angiogenesis in interval sentinel lymph nodes in melanoma could be used as a good predictive marker to distinguish interval positive sentinel lymph nodes with micrometastasis from interval positive lymph nodes with macrometastasis subgroups.     

Notexin对小鼠体内CD8+ T淋巴细胞活性的干扰作用

目的　探讨肌肉注射Notexin是否影响C57BL/6小鼠骨骼肌引流淋巴结内的外源性CD8+ T细胞（OT-I细胞）的活性和增殖。  方法　分别采用Notexin注射或机械挤压法制备B6小鼠的胫骨前肌（TA）急性肌损伤模型,并获得性转移（adoptive transfer, i.v.）OVA特异的OT-I细胞（CFSE标记）,随后肌注可溶性OVA蛋白。收集损伤侧TA引流淋巴结 (腘、腹股沟淋巴结),流式分析OT-I细胞的增殖程度。OVA静脉内注射免疫B6鼠,收集激活的脾脏树突状细胞（cDCs）,与CFSE标记的OT-I细胞体外联合培养,并添加不同稀释度的Notexin, 流式检测OT-I细胞的活性和增殖。 结果　CFSE的荧光递减结果证实,机械挤压损伤鼠TA引流淋巴结内OT-I细胞迅速活化增殖,但Notexin诱发的肌损伤小鼠引流淋巴结内OT-I细胞在4 d时无增殖反应,7 d的增殖率与非注射组无显著差异。与活化的cDCs细胞共培养的OT-I细胞活性良好,增殖显著,但即使添加高度稀释（1：1000）的Notexin也会严重干扰OT-I细胞的活性和增殖。  结论　肌内注射Notexin注射将干扰CD8+ T细胞的活性,这表明蛇毒血清诱导的骨骼肌损伤模型不适用于肌损伤诱发的T细胞功能改变的相关研究。     

Size, CD4 and CDS Marker Profiles and Functions of Lymphocyte Subpopulations in Mucosal-Associated Lymph Nodes

We analyzed phenotypic and functional characteristics of T cell populations in mucosal-associated supramammary and mesenteric lymph nodes in goats. Here we demonstrate, by flow cytometry, quantitative differences in CD4 and CD8 T cell subsets among large and small mucosal-associated lymphocyte populations and their differential regulatory activities on resident lymph node B cells stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen. The CD4/CD8 T cell ratio was Tower in mesenteric lymph nodes (1.46) when compared to that of supramammary lymph nodes (2.18), Analysis of large and small lymphocyte subpopulations from lymph nodes showed nearly 62% of the lymphocytes from mesenteric lymph nodes being of large cell phenotype with CD4/CD8 ratios of 1.34. In contrast, large cell subpopulations in supramammary lymph nodes showed a significantly lower number (50%) with a higher CD4/CD8 ratio of 2.05. Functionally, mesenteric lymph node T cells, isolated by nylon wool, showed heightened suppressive activity in mitogen-driven B cell proliferation responses, whereas T cells from supramammary lymph nodes were stimulatory. These findings clearly demonstrate distinctive functional properties between resident T cell populations of supramammary and mesenteric lymph nodes, suggesting that different proportions of T cell subsets in these; nodes are activated and thus regulate regional immune responses via different pathways.     

Size, CD4 and CD8 marker profiles and functions of lymphocyte subpopulations in mucosal-associated lymph nodes.

We analyzed phenotypic and functional characteristics of T cell populations in mucosal-associated supramammary and mesenteric lymph nodes in goats. Here we demonstrate, by flow cytometry, quantitative differences in CD4 and CD8 T cell subsets among large and small mucosal-associated lymphocyte populations and their differential regulatory activities on resident lymph node B cells stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen. The CD4/CD8 T cell ratio was lower in mesenteric lymph nodes (1.46) when compared to that of supramammary lymph nodes (2.18). Analysis of large and small lymphocyte subpopulations from lymph nodes showed nearly 62% of the lymphocytes from mesenteric lymph nodes being of large cell phenotype with CD4/CD8 ratios of 1.34. In contrast, large cell subpopulations in supramammary lymph nodes showed a significantly lower number (50%) with a higher CD4/CD8 ratio of 2.05. Functionally, mesenteric lymph node T cells, isolated by nylon wool, showed heightened suppressive activity in mitogen-driven B cell proliferation responses, whereas T cells from supramammary lymph nodes were stimulatory. These findings clearly demonstrate distinctive functional properties between resident T cell populations of supramammary and mesenteric lymph nodes, suggesting that different proportions of T cell subsets in these nodes are activated and thus regulate regional immune responses via different pathways.     

Size,CD4 and CDS Marker Profiles and Functions of Lymphocyte Subpopulations in Mucosal-Associated Lymph Nodes

We analyzed phenotypic and functional characteristics of T cell populations in mucosal-associated supramammary and mesenteric lymph nodes in goats. Here we demonstrate, by flow cytometry, quantitative differences in CD4 and CD8 T cell subsets among large and small mucosal-associated lymphocyte populations and their differential regulatory activities on resident lymph node B cells stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen. The CD4/CD8 T cell ratio was Tower in mesenteric lymph nodes (1.46) when compared to that of supramammary lymph nodes (2.18), Analysis of large and small lymphocyte subpopulations from lymph nodes showed nearly 62% of the lymphocytes from mesenteric lymph nodes being of large cell phenotype with CD4/CD8 ratios of 1.34. In contrast, large cell subpopulations in supramammary lymph nodes showed a significantly lower number (50%) with a higher CD4/CD8 ratio of 2.05. Functionally, mesenteric lymph node T cells, isolated by nylon wool, showed heightened suppressive activity in mitogen-driven B cell proliferation responses, whereas T cells from supramammary lymph nodes were stimulatory. These findings clearly demonstrate distinctive functional properties between resident T cell populations of supramammary and mesenteric lymph nodes, suggesting that different proportions of T cell subsets in these; nodes are activated and thus regulate regional immune responses via different pathways.     

The effect of human placental protein 14 (PP14) on the production of interleukin-1 from mitogenically stimulated mononuclear cell cultures.

Twenty-four hours after skin painting mice on the flank with the contact sensitizer fluorescein isothiocyanate (FITC), the number of dendritic cells (DC) increased sharply, not only in draining but also in contralateral (CLN) and distant lymph nodes. High levels of antigen were detected on up to 50% of DC isolated from draining lymph nodes (DLN), and these cells were potent stimulators of naive T cells in vitro. Less than 3% of DC from contralateral and distant lymph nodes carried detectable antigen and did not induce significant T-cell proliferation. A significant number of DC had migrated to draining, contralateral and distant lymph nodes without acquiring detectable antigen. This indicates that there is a systemic signal causing the movement of DC to lymph nodes. This appears to be independent of mature T cells, as the systemic migration of DC also occurred in nude mice.     

Plasmacytoma of lymph node. Recurrent lymphadenopathy terminating in plasma cell dyscrasia with polyneuropathy and endocrine disturbances

A case with lymphadenopathy of the left side of the neck in a 38-year-old male is described. He had a history of several relapses of about 10 years duration. Swollen lymph nodes were histologically similar to those of the hyaline-vascular type of Castleman's disease, but contained clear-cut lymph sinus and a sheet-like proliferation of plasma cells. Lymph follicles showed proliferation and atrophic germinal centers, in which cellular hypertrophy in the wall of ramifying small blood vessels, called angiosclerosis, was frequently encountered. During its progress, the patient developed plasmacytoma of the lymph nodes with varied clinical manifestations such as polyneuropathy, disturbance of gait, unusual perspiration, hirsutism, gynecomastia, bilateral papilledema, and albumino-cytologic dissociation in cerebrospinal fluid.     

In vitro and in vivo stimulation of the murine immune system by AGM-1470, a potent angiogenesis inhibitor.

AGM-1470, a potent angiogenesis inhibitor, is already engaged in phase I clinical trials because of its effectiveness to restrain tumor growth and its lack of major side effects. Recently, we showed that AGM-1470 stimulates in vitro human B lymphocyte proliferation through T lymphocytes. These data prompted us to explore the in vivo effects of AGM-1470 on the immune system in a mouse model. In this study, we showed that AGM-1470, in synergy with phytohemagglutinin, stimulates the proliferation of murine lymphocytes isolated from lymph nodes. This effect was similar to the one observed with human lymphocytes. When injected subcutaneously or intraperitoneally into mice at pharmacological doses, AGM-1470 induced a significant increase of axillary and mesenteric lymph nodes, respectively. Histological and morphological analyses showed that this phenomenon is mostly due to a hyperplasia of the germinal centers. On average, the area of the germinal center of lymph nodes from AGM-1470-treated mice were three times larger than in lymph nodes from control mice. Interestingly, no effect was observed when AGM-1470 was injected subcutaneously into T-deficient nude mice. Our data demonstrate that AGM-1470 stimulates B cell proliferation in vivo as suggested by the in vitro experiments. This effect should be taken into account in the follow-up of patients treated with this molecule and calls for additional studies to determine the biological consequences of such a stimulation on the host immune system.     

Lymphatic mast cell response and effect of compound 48/80 on popliteal lymph node reaction in rats following intracutaneous injection ofStaphylococcus aureus

To investigate the significance of mast cells in the popliteal lymph node during the development of an inflammatory response, rats were inoculated with 12×10⁷ colony-forming units ofStaphylococcus aureus in the hind foot pad. Numerical changes in mast cells were then measured in the corresponding popliteal lymph node. Six days after inoculation, despite the enlargement of the responding lymph node, a marked decrease in granulated mast cell number, relative to the contralateral node, was observed in the cortical and medullary compartments. Popliteal lymph nodes from rats treated with compound 48/80 and then inoculated withS. aureus showed a higher cortical and medullary hypertrophic response and a significant increase in degranulated/weakly basophilic mast cell number in the lymph node tissue. The findings suggest that (1)Staphylococcus aureus induces a reduction in granulated mast cell number in the cortical and medullary compartments of regional lymph nodes; (2) pretreatment with compound 48/80 appears to contribute to the lymphoid cell proliferation and the hypertrophic response of lymph nodes induced byS. aureus; and (3) granulated mast cells have a regulatory role on lymphoid cell proliferation.     

Lymphadenopathy during cytomegalovirus-induced mononucleosis in guinea pigs

Hartley guinea pigs infected with guinea pig cytomegalovirus (GP-CMV) develop a mononucleosis syndrome during primary infection that is similar to that seen in immunocompetent humans. In the present study this animal model of human disease was used to investigate the sequential changes in the lymph nodes during the course of primary GP-CMV infection. Infectious virus could be isolated from the nodes up to eight weeks after inoculation. When compared with nodes of control animals, the nodes of GP-CMV-infected animals were found to be enlarged up to a year after infection. During the first ten days of infection, histologic changes due to virus proliferation and immune stimulation of the paracortical areas of the lymph node, in a diffuse hyperplasia pattern, were noted. Although typical cytomegalovirus inclusions were seen only rarely, many cells demonstrated intranuclear staining using an avidin-biotin immunoglucose-oxidase histochemical reaction for GP-CMV. During late acute and chronic infection, the lymph nodes showed immune stimulation of the germinal centers, in the pattern of follicular hyperplasia. Specific histologic changes related to active virus proliferation were not seen after the early acute phase.     

Virus-associated hemophagocytic syndrome: identification of an immunoproliferative precursor lesion

Virus-associated hemophagocytic syndrome (VAHS) is a nonneoplastic, generalized histiocytic proliferation with marked hemophagocytosis associated with a systemic viral infection. Histologic studies of lymph nodes usually show lymphoid depletion and histiocytic proliferation. In this report we describe the case of a patient with Epstein-Barr virus-associated VAHS in which initial lymph node biopsy samples showed an immunoproliferative lesion that preceded the usual generalized histiocytic proliferation. This finding suggests that some cases of VAHS may have an immunoproliferative precursor lesion.     

Langerhans cell sarcoma involving gallbladder and peritoneal lymph nodes: a case report

Langerhans cell sarcoma (LCS) is a rare proliferation of Langerhans cells with overtly malignant cytologic features and spreads aggressively. LCSs show a multiorgan involvement, including skin, lymph nodes, lung, and bone. The authors report an LCS in a 74-year-old woman that involved the gallbladder and the peritoneal lymph nodes. Imaging revealed a tumor in the gallbladder and the peritoneal lymph nodes. The tumor cells were positive for CD1a, S-100 protein, and Langerin (CD207). Although the ultrastructural analysis failed to demonstrate any Birbeck granules, the histomorphological and immunohistochemical findings supported the diagnosis of LCS. After surgical resection, she showed no recurrent or metastatic signs for 8 months without any other adjuvant therapy. This is the first case of LCS involving the gallbladder and the peritoneal lymph nodes. This report also includes a review of the literature concerning this rare disease.     

引流肺淋巴的淋巴结内灰尘颗粒的分布和结构变化

目的 :研究灰尘颗粒在引流肺淋巴的淋巴结内的分布和淋巴结的组织变化。方法 :取成人和儿童肺门淋巴结、气管支气管淋巴结和气管旁淋巴结 ,石蜡切片。取肺切除术患者的肺门淋巴结作超薄切片。结果 :尘细胞和灰尘颗粒分布于淋巴结被膜、淋巴窦和髓索内。肺门淋巴结和气管支气管淋巴结的光密度比气管旁淋巴结高 ,成人肺门淋巴结、气管支气管淋巴结和气管旁淋巴结的光密度高于儿童的淋巴结。成人淋巴结的血管密度与儿童淋巴结之间存在着显著性差异。间质胶原纤维增生。结论 :在引流肺淋巴的淋巴结内 ,肺门淋巴结和气管支气管淋巴结内的灰尘颗粒明显多于气管旁淋巴结 ,成人淋巴结灰尘颗粒比儿童多。在成人 ,灰尘颗粒引起淋巴结的淋巴组织减少 ,纤维组织和血管增生     

Smooth muscle proliferation in the hilum of superficial lymph nodes

Summary A retrospective survey to study hilar smooth muscle proliferation was performed on 410 superficial lymph nodes from 130 patients. Smooth muscle proliferation of variable degree was found in a total of 32 patients, affecting both inguinal and axillary nodes. A slight predominance of inguinal lesions was noted, and a higher proportion of nodes from male patients was affected. The smooth muscle proliferation was not age related nor was it associated with metastatic carcinoma. An association between smooth muscle proliferation and prominent hilar vascularity was found. In individual cases where several nodes had been removed, there was a tendency for more than one node to show smooth muscle proliferation, suggesting that there is a locally acting diffusible aetiological agent. We think the smooth muscle proliferation we have described is of vascular origin, and that it may reflect a previous inflammatory reaction.     

Immunological approach in the evaluation of regional lymph nodes of patients with squamous cell carcinoma of the head and neck.

In cancer, regional lymph node (LN) cells are one of the first components of the immune system to have contact with tumor cells or their products. Therefore, the phenotype and functional properties of hematopoietic cells present within the tumor-draining LN are important to understanding their role in the control of malignant cells. Based on the locoregional metastatic behavior of squamous cell carcinoma of the head and neck (SCCH&N) region, we analyzed tumor-draining lymph nodes from SCCH&N patients to obtain insights into regional tumor immunity. Using a three-color fluorescent labeling technique, surface antigen expression was visualized in mononuclear cells of lymph nodes that were obtained from head and neck cancer patients and compared to mononuclear cells of normal lymph nodes. Cell cycle analyses were performed using propidium iodide. Proliferation after phytohemagglutinin stimulation was measured by a sodium tetrazolium-based assay. LN histology was correlated with flow cytometric findings. Regional lymph nodes of head and neck cancer patients undergo morphologic and functional changes. Flow cytometry revealed a decrease in CD8(+) T cells and in some lymph nodes the presence of second or third populations of larger cells with distinct size and granularity that expressed both T (gammadelta/alphabeta) and different natural killer cell markers. Moreover, cell cycle analyses and proliferation assays showed a diminished response to mitogenic stimuli. These changes were found in both metastatic and hyperplastic lymph nodes from head and neck cancer patients; however, no alterations were found in control lymph nodes or peripheral blood mononuclear cells from noncancer patients. The immune alterations detected in lymphocytes present within the draining lymph nodes of head and neck cancer patients may improve our understanding of how tumor cells escape host immunosurveillance. However, this dysfunction in local draining lymph nodes may not be detected systemically.