Lymph Node: Metastasis and Cancer Spread

Introduction

The lymph nodes are the most common sites of the metastasis of cancer. The metastasis refers to the spread of cancer to lymph nodes (consisting lymphatic system). The lymphatic system in the body is composed of lymph nodes. The function of the lymphatic system is to maintain immunity and fluid balance in the body. Cancer, chronic inflammation, and infections can all weaken immunity by causing malfunction in draining lymph nodes and lymphatic arteries. In addition, cancer cells spread through lymphatic arteries and spread through draining lymph nodes. Metastatic lymph nodes consequently experience immunological suppression. As a result, the spread of cancer weakens the body's immune system through lymph node metastases.

What Is Lymphatic System?

The lymphatic system is made up of lymphatic vessels and lymph nodes. The lymphatic system maintains the body's immune system and fluid balance.

Following are the function of the lymphatic system:

• The lymphatic system carries waste products and antigens from the extracellular fluid and produces lymph. Lymph is produced by lymphatic vessels by absorbing interstitial fluid.

• Lymph is transported by the lymphatic vessels and drains in the lymph nodes.

• Lymph nodes initiate adaptive immune responses. Thus, lymph returns to the blood after being monitored by lymph nodes.

• Lymph protects from the entry of the antigens (infection).

What Are Lymph Nodes?

Lymph nodes are the important organ involved in developing the adaptive immune response. It is a kidney-shaped organ in the lymphatic system. The lymph nodes are located in the body, such as the neck, armpits, chest, groin (area between the genitals), and upper abdomen region.

Following are the function of the lymph nodes:

• The lymph travels to lymph nodes via collecting lymphatic channels and carries local information from tissues to each lymph node.

• The lymph nodes help promote the efficient production of adaptive immune responses by allowing the contact of antigen-presenting cells with lymphocytes (white blood cells that help fight against the antigen).

• The lymph nodes produce two lymphocyte types: T-cells (T-lymphocytes) and B-cells (B-lymphocytes). B-cells produce antibodies that fight against viruses, bacteria, and other infections.

• T- lymphocytes help in adaptive immune response, which helps to fight against specific infections.

What Is Lymph Node Metastasis?

When cancerous tumor cells enter lymph nodes and spread to other body organs, they are called lymph node metastasis. A tumor refers to a rapidly growing cancerous cell mass. Lymph node metastases are a long-recognized phenomenon by which cancer cells enter the lymphatic vessels and move to tumor-draining lymph nodes. The tumor cells develop infection inside the tumor-draining lymph nodes and leave lymph nodes to further spread to other body organs.

The following steps explain the process of lymph node metastasis:

• Migration of Tumor Cells to a Draining Lymph Node - The cancerous cells hijacked the protection mechanism of the lymph nodes. The major valve structures (button junction) of each lymph node open when interstitial fluid pressure (IFP) exceeds and permits the entry of lymphocytes (white blood cell component) under normal physiological conditions. Tumors have a high IFP. Therefore, cancer cells may mechanically enter the lymphatic capillaries more easily. Cancer cells can be carried to lymph nodes by lymph flow once they have entered the draining lymphatic channels. The inhibition of lymphatic contraction results in aberrant flow in lymphatic channels that drain tumors. The lymph flow has a far lower fluid shear force than blood flow. The decreased lymphatic contraction may further reduce the shear stress and increase tumor cell survival. According to a recent study, human melanoma (type of skin cancer) tumor that initiated lymph node metastasis had higher IFP, high density of lymphatic vessels around the tumor, and high growth factor expression. This growth factor expression promotes lymph node metastasis.
• Survival of Tumor Cells in Draining Lymph Nodes - Although immunosuppression in tumor-draining lymph nodes is well understood, it is still unclear how cancer cells can destroy an organ rich in immune cells and avoid being destroyed. The strategy used by cancer cells to suppress the immune system, which is monitored by lymph nodes, is to inhibit the lymphocyte expression or the fighting capacity of T cells. Once cancer cells enter tumor-draining lymph nodes, they convert the environment into more permissible surroundings for their growth and survival. Lymph nodes consist of immune cells which maintain the balance between producing the immune response against pathogens and tolerance against self-infectious agents. This critical balance is made by different immune cells. Cancer cells change these immune cells' structures to promote metastatic growth and survival. Tumor cells utilize the existing lymph node blood vasculature to secure a nutrient supply to survive.
• Lymph Node Metastases Spread Further to Other Organs - Distant metastasis refers to the spread of tumor cells to the lungs, abdomen, and other organs. Although not all metastatic cells enter the lymph node, they end up in distant metastasis. Lymph node metastasis can contribute to distant metastasis, and the ability of lymph node metastasis to initiate distant metastasis has recently come to light. Several studies showed that the origin of distant metastasis is lymph nodes.

What Happens If Cancer Spreads to Lymph Nodes?

When cancer spreads to lymph nodes, they destroy the ability of the lymphatic system to produce an adaptive immune response. Therefore, patients with lymph node metastases become weak and unable to fight against further exposure to infection. In addition, lymph nodes can be the origin of distant metastases and affect other body organs. A crucial location for inducing antitumor immunity is tumor-draining lymph nodes. However, due to drainage, tumor-draining lymph nodes also become colonized by cancer cells that have spread to other organs and suppress the immune system. When cancer spreads to lymph nodes, it can cause lymphoedema. Lymphedema refers to swelling in the lymph nodes, usually observed in the patient's limbs. Lymph node metastasis can be the origin of hematogenous (spread in the blood) spread. The spread of cancerous cells can be fatal and life-threatening.

How Can Lymph Node Metastasis Be Treated?

Once the diagnosis is made, the lymph node metastasis can be treated by excision of the lymph nodes. The combination of chemotherapy and radiation therapy can further prevent disease progression and preserve the function of lymph nodes.

The following are the ways to treat lymph node metastases:

• Surgical Removal of Lymph Nodes - Surgical removal of the targeted lymph node is adapted to treat lymph node metastasis. Once the diagnosis is made, this suspected lymph node is marked. It is advised to surgically remove the tumor-draining lymph node since lymph node metastasis may be a factor of distance metastasis.

• Chemotherapy - Eliminating cancer cells in lymph nodes can be done by delivering enriched therapeutic agents. Nanosized particles are made to introduce therapeutic agents in the lymph node as the structure of lymph nodes does not permit the entry of these agents. When administered, submucosal pegylated liposomal Doxorubicin, often known as Doxil, has demonstrated effectiveness in localized lymph nodes in patients with stomach cancer. When administered intravenously, the combination of Motixafortide and Pembrolizumab enhanced chemotherapy outcomes in metastatic pancreatic cancer.

• Radiation Therapy - Radiation therapy can be used further to prevent disease progression while preserving immunity.

Conclusion

Lymph node metastasis can be fatal and life-threatening as it can spread into the blood and affect other body organs. Therefore, addressing lymph node metastasis at the right time may help lessen the burden of systemic metastasis. The prompt diagnosis is essential to research the origin of lymph node metastasis. Introducing new therapies for lymph node metastasis could have significant therapeutic advantages. The ultimate goal of treating metastatic lymph nodes is to eliminate the ability of the disease to spread from lymph nodes while maintaining systemic anti-cancer immune activity and avoiding lymphoedema. The challenging issue of lymph node metastasis must be resolved by prompt diagnosis and proper medical intervention.