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 lymphoma cells were subcutaneously injected. Expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-2 as well as IL-10 expression in draining lymph nodes (LNs) was significantly reduced in kCYC mice after tumor inoculation. Moreover, decreased levels of tumor-associated antigens were detected in draining LNs in kCYC mice, together with impaired antigen presentation. CD8+ T cells in draining LNs derived from kCYC mice bearing B16 melanoma also showed significantly decreased cytotoxic activity in vitro. Finally, tumor suppression activity of CD8+ T cells derived from kCYC mice bearing B16 melanoma was reduced when adoptively transferred to naive wild-type mice. In summary, these findings suggest that lymphatic transport is essential in generating optimal tumor-specific immune responses mediated by CD8+ T cells.
Highlights
Tumor growth and metastasis of cancer involve autonomous tumor cell growth and host–tumor interactions [1]
To evaluate the effects of lymphatic dysfunction on primary tumor growth, B16 melanoma cells were injected subcutaneously into kCYC and wildtype (WT) mice, and tumor growth was determined on days 3, 7, 10, and 14
To evaluate the effects of lymphatic dysfunction on primary tumor growth, EL-4 lymphoma cells were injected subcutaneously into kCYC and WT mice in the same manner as B16 melanoma cells, and tumor growth was determined on days 3, 7, 10, and 14
Summary
Tumor growth and metastasis of cancer involve autonomous tumor cell growth and host–tumor interactions [1]. Function of each of these cell types in tumor immunity has been examined, antitumor activity of immune cells in the context of lymphatic dysfunction is yet to be fully elucidated. The lymphatic system collects extravasated fluid, macromolecules, and cells of the immune system within tissues and returns them to the blood circulation [5]. Lymphedema occurs when there is interstitial accumulation of protein-rich fluid and subsequent inflammation, adipose tissue hypertrophy, and fibrosis. More attention has been paid to this condition since it is a relatively common complication following surgical treatment of malignancy [6]. Reduced tissue immune surveillance secondary to lymphatic dysfunction may cause cancer. Lymphatic vessels are critical for transporting tissue-resident DCs and other immune cells as well as interstitial fluid to the lymph nodes (LNs), which is important in immunity against infectious agents and malignancy. The role of lymphatic drainage on local immunity has been receiving attention, only few studies were performed using mouse models [13,14,15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
