2015
DOI: 10.18632/oncotarget.4018
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Abstract: Tumor growth and metastasis of cancer involve autonomous tumor cell growth and host-tumor interactions. While tumor-specific immunity has been intensively studied in vitro, dynamic roles of lymphatic transport on tumor immunity in vivo have not been fully elucidated. In this study, we examined tumor growth and anti-tumor immune responses using kCYC mice, which demonstrate severe lymphatic dysfunction. Primary tumor growth was augmented in kCYC mice (compared to wild-type mice) when B16 melanoma or EL-4 lymphom… Show more

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Cited by 42 publications
(38 citation statements)
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“…In our study, less macrophages and leukocytes were recruited to the tumor vicinity together with a significant downregulation of macrophage-associated cytokines, pointing to a weakened innate anti-tumor immune response. This is in accordance with recent data demonstrating augmented melanoma and lymphoma growth, as well as decreased local lymph node inflammation, in kCYC mice with reduced lymphangiogenesis [15]. It has been established previously that the humoral immune response on the trunk is not influenced by the Chy mutation [28], and our current finding of no difference in the number of peritumoral adaptive immune cells between Chy and wt mice is in line with these observations.…”
Section: Discussionsupporting
confidence: 94%
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“…In our study, less macrophages and leukocytes were recruited to the tumor vicinity together with a significant downregulation of macrophage-associated cytokines, pointing to a weakened innate anti-tumor immune response. This is in accordance with recent data demonstrating augmented melanoma and lymphoma growth, as well as decreased local lymph node inflammation, in kCYC mice with reduced lymphangiogenesis [15]. It has been established previously that the humoral immune response on the trunk is not influenced by the Chy mutation [28], and our current finding of no difference in the number of peritumoral adaptive immune cells between Chy and wt mice is in line with these observations.…”
Section: Discussionsupporting
confidence: 94%
“…This is in line with a previous report in non-tumor bearing Chy mice [28]. Lymphatic peritumoral drainage transports cytokines and antigens to the lymph nodes to elicit an immune response [29], and this process is impaired in mice with reduced lymphangiogenesis [15]. In our study, less macrophages and leukocytes were recruited to the tumor vicinity together with a significant downregulation of macrophage-associated cytokines, pointing to a weakened innate anti-tumor immune response.…”
Section: Discussionsupporting
confidence: 92%
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“…These results corroborate recent work in another model of lymphatic dysfunction in which the Kaposi's sarcoma-associated herpesvirus latent-cycle gene, k-cyclin, is expressed under the control of the VEGFR-3 promoter (53). In these mice, antigen presentation in dLNs was impaired and CD8 + T cells demonstrated suppressed cytotoxicity (54). This highlights the important role of dLNs in antitumor immunity (22,43).…”
Section: Discussionmentioning
confidence: 84%
“…They are also strongly influenced by tumor‐derived factors, such as cytokines . Therefore, impairment of these lymphoid organs can decrease antitumor immunity …”
Section: Introductionmentioning
confidence: 99%