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Updated: May 31, 2026
Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis
Published on: January 26, 2024
Phenotypic alterations in the immune system and tolerance induction in tumor-draining lymph nodes
Zohreh Koohini1, Mansoureh Karimi Kakh1, Zeinab Rajabian2
1Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Abstract:
The cause of 90% of all cancer-related fatalities is metastasis. There are two main pathways for the spread of cancer cells: the blood and lymphatic systems. The underlying mechanism of lymphatic metastasis has been well established. However, our understanding of the molecular basis of lymphatic metastasis is still incomplete. Conceptually, cancer cells invade lymphatic vessels (LVs), passively disseminate towards lymphatic nodes, migrate to sentinel lymphatic nodes (SLNs; the first LNs to which cancer cells spread from the primary tumor), and then enter the bloodstream. Before arrival, cancer cells release specific soluble factors that modulate the SLN microenvironment, creating an immunosuppressive environment. After colonization, cancer cells suppress anti-tumor immunity by stimulating regulatory T cells, inhibiting dendritic cell and CD8+ T cell function, and promoting the release of immunosuppressive cytokines. SLNs serve as a microanatomical site for metastasis and play a crucial role in immune modulation. Developing new strategies to reverse tumor-induced remodeling of SLNs may reactivate immunity and reduce accumulation and metastasis. This review discusses the immunological changes induced by tumors in tumor-draining LNs (TDLNs). We also explore their reciprocal relationship and their impact on metastasis and LN immunity, demonstrating how a proper understanding of events occurring in TDLNs can create new opportunities for cancer immunotherapy.
Insights
Metastasis, the spread of cancer, often occurs via lymphatic vessels. Tumors create an immunosuppressive environment in sentinel lymph nodes, hindering anti-tumor immunity and promoting cancer spread.
Area of Science:
- Oncology
- Immunology
- Cancer Metastasis Research
Background:
- Metastasis causes 90% of cancer fatalities, with lymphatic spread being a key pathway.
- While lymphatic metastasis mechanisms are known, the molecular basis remains unclear.
- Cancer cells spread through lymphatic vessels (LVs) to sentinel lymph nodes (SLNs), impacting immunity.
Purpose of the Study:
- To review immunological changes in tumor-draining lymph nodes (TDLNs) induced by tumors.
- To explore the relationship between TDLNs, metastasis, and lymph node immunity.
- To identify opportunities for cancer immunotherapy based on TDLN events.
Main Methods:
- Literature review of immunological changes in TDLNs.
- Analysis of molecular mechanisms of lymphatic metastasis.
- Exploration of the tumor-lymph node microenvironment.
Main Results:
- Tumors induce immunosuppression in SLNs by modulating the microenvironment.
- Cancer cells promote immune evasion through various cellular and cytokine-mediated mechanisms.
- SLNs are critical sites for both metastasis and immune modulation.
Conclusions:
- Understanding tumor-induced immunological changes in TDLNs is crucial for cancer progression.
- Reversing tumor-induced remodeling in SLNs may enhance anti-tumor immunity.
- Targeting TDLN events offers new avenues for cancer immunotherapy.
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