According to a recent article in Genetic Engineering News, findings by scientists at the University of Boston’s School of Medicine and Massachusetts General Hospital (MGH) have uncovered two plausible reasons why cancer cells are able to resist an attack by immune cells.
Dr. Timothy Padera, a radiation oncology investigator at MGH, began by explaining that as cancer progresses, it usually spreads to the lymph nodes. These glands are part of the lymph system that transports waste material and nutrients between the bloodstream and body tissues.
Lymph nodes play an important role in the immune system’s defense against tumors. But when cancer cells metastasize to lymph nodes, these cells can avoid being destroyed.
Dr. Padera further noted that the immune system is capable of killing cancer cells. But what they did not know is why the immune system allows cancer cells to survive rather than attacking them.
The scientists now believe that one answer lies in a physical force in metastatic lymph nodes called “solid stress” that disturbs the immune system’s ability to fight the cancer cells. Solid stresses are generated through cancer cell growth which disrupts the tissue structure and compresses lymphatic vessels and blood in primary tumors.
The scientists determined that if they could control solid stress in the lymph nodes, that would facilitate the T-cells (T lymphocytes) in their journey into the lymph nodes and thus improve anticancer immunity. T-cells are a type of white blood cell that is part of the immune system. They fight infection and also fight cancer.
The second answer pertains to studies that found losartan, an antihypertensive drug, can ease some of the solid stress effects that will in turn increase the number of lymphocytes (a type of immune cell) entering metastatic lesions.
Relieving solid stress in mice created a significant increase in lymphocytes present in lymph-node metastases.
A Blood Pressure Medication and Cancer?
A medication called losartan that is used to reduce blood pressure also reduces solid stress. This results in an increase in immune-boosting T-cells and blood vessels that form in node metastases.
Colonizing Lymph Nodes
Cancer cells invade nearby lymph vessels then migrate to lymph nodes and transition to colonized tumors. If the cancer cells continue to grow in the lymph nodes, they can reach other organs thus driving tumor progression.
Compressing Lymph Nodes
The team created a device that compresses lymph nodes in an effort to simulate the growth of metastatic lymph nodes. As they used compressive force on the lymph nodes, it was evident that the physical force caused disruption of the T-cells’ entry into the lymph nodes.
The new compression device is able to reproduce various aspects of macrometastatic nodal lesions. These lesions that have spread to other parts of the body have been shed from the original tumor. The compression causes lymph node vessels to collapse thereby reducing opportunities for lymphocytes to gain access into lymph nodes.
Conclusion
Dr. Padera noted that when the scientists worked with tissue from patients and from mouse models, they discovered that if lymphocytes are absent from nodal lesions, the result is solid stress resulting from lesion growth.
After measuring solid stress in lymph nodes containing metastatic lesions, the scientists determined that when solid stress resides in lymph node tumors both T-cell maneuvering and blood flow will be impaired.
Therefore, reducing solid stress could potentially improve T cells penetrating tumors. The drug losartan has reduced solid stress by reducing collagen in metastatic lesions after the removal of a primary tumor.
Looking forward
They found that as cancer cells grow within the lymph nodes, the cells alter the lymph node and disable responses by the immune system. By forming a better understanding of how cancer cells can disable the way lymph nodes’ function, the team hopes to work with lymph nodes in the future in their fight against cancer.
