Reprogramming of sentinel lymph node microenvironment during tumor metastasis

• Published in: Journal of biomedical science 2022-10, Vol.29 (1), p.1-84, Article 84
• Main Authors: Li, Yen-Liang, Hung, Wen-Chun
• Format: Article
• Language: English
• Subjects: Antibodies; Antigen presentation; Antigens; B cells; Biological products; Biopsy; Blood; Blood vessels; Breast cancer; Cancer; Cancer vaccines; CD8 antigen; Chemotherapy; Circulatory system; Colonization; Colorectal cancer; Cytokines; Dendritic cells; Immune; Immune checkpoint; Immunity; Immunomodulation; Lymph node; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Medical prognosis; Melanoma; Metastases; Metastasis; Microenvironment; Microenvironments; Nanoparticles; Nanotechnology; Patients; Review; Suppressor cells; T cells; Thyroid cancer; Tumors; Vascular endothelial growth factor
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-022-00868-1

Metastasis is a major cause of death in patients with cancer. The two main routes for cancer cell dissemination are the blood and lymphatic systems. The underlying mechanism of hematogenous metastasis has been well characterized in the past few decades. However, our understanding of the molecular basis of lymphatic metastasis remains at a premature stage. Conceptually, cancer cells invade into lymphatic capillary, passively move to collecting lymphatic vessels, migrate into sentinel lymph node (SLN;, the first lymph node to which cancer cells spread from the primary tumor), and enter the blood circulatory system via the subclavian vein. Before arriving, cancer cells release specific soluble factors to modulate the microenvironment in SLN to establish a beachhead for successful colonization. After colonization, cancer cells inhibit anti-tumor immunity by inducing the recruitment of regulatory T cell and myeloid-derived suppressor cells, suppressing the function of dendritic cell and CD8 + T cell, and promoting the release of immunosuppressive cytokines. The development of novel strategies to reverse cancer cell-triggered SLN remodeling may re-activate immunity to reduce beachhead buildup and distant metastasis. In addition to being a microanatomic location for metastasis, the SLN is also an important site for immune modulation. Nanotechnology-based approaches to deliver lymph node-tropic antibodies or drug-conjugated nanoparticles to kill cancer cells on site are a new direction for cancer treatment. Conversely, the induction of stronger immunity by promoting antigen presentation in lymph nodes provides an alternate way to enhance the efficacy of immune checkpoint therapy and cancer vaccine. In this review article, we summarize recent findings on the reprogramming of SLN during lymphatic invasion and discuss the possibility of inhibiting tumor metastasis and eliciting anti-tumor immunity by targeting SLN.