Phenotypic alterations in the immune system and tolerance induction in tumor-draining lymph nodes

The cause of ۹۰% 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 CD۸+ 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.

کلیدواژه ها:

Cellular reprogramming ، Immune tolerance ، Neoplasm metastasis ، Sentinel lymph nodes ، Tumor Microenvironment