“Solid Stress” Keeps Immune System from Killing Off Cancer Cells in the Lymph Nodes, Study Says

Cancer

Lymph nodes play a very important role in the body’s immune system and are vital to the body’s ability to respond to and kill off cancerous tumors. In theory, therefore, the lymph nodes should not be a place where cancer likes to hang out. And yet, for some reason, they are.

It may seem like a paradox, but cancer cells often make their way to the lymph nodes and develop into tumors there, where they manage to avoid being killed by the body’s immune cells. How does this happen?

Researchers at Massachusetts General Hospital (MGH) and Boston University School of Medicine wondered the same thing, so they began looking into the mechanisms behind this strange phenomenon.

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“We know that lymph nodes are often the first place cancer spreads as it progresses. We also know that our immune system can attack and kill cancer cells,” explains senior and co-corresponding author Timothy P. Padera, Ph.D., an investigator in Radiation Oncology at MGH. “One of the perplexing questions that has been at the core of the recent work in my lab is how can organs that generate our immune responses—lymph nodes—permit cancer cells to survive and take them over instead of attacking them? This was the driving motivation behind this study.”

The researchers analyzed breast, colon, and head and neck tissues from cancer patients and compared them to animal models of breast cancer metastasis in the lymph nodes. As expected, they found that there were large number of immune cells called T cells in the lymph nodes. However, the T cells failed ot penetrate into tumors in the lymph nodes.

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By measuring the force, known as solid stress, inside the lymph nodes, they learned that this pressure may be what causes the T cells to have trouble killing off cancer cells.

“We hypothesized that solid stress in lymph node tumors can impair both blood flow and the T cell trafficking capacity of blood vessels in lymph nodes,” says lead and co-corresponding author Dennis Jones, Ph.D., an assistant professor of Pathology & Laboratory Medicine at the Boston University School of Medicine.

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The researchers then developed a device to compress the lymph nodes to simulate the growth of lymph node tumors. They found a clear link between the physical force applied to the lymph nodes and the disruption of T cell entry into the lymph nodes.

“Our findings indicate that as cancer cells grow in the lymph node, they reorganize and alter the lymph node, disabling critical functional responses of the immune system,” says Padera. “By understanding how cancer cells are disabling lymph node function, we hope to fight back to help the lymph nodes generate anti-cancer immune responses, which will help fight cancer cells everywhere in the body.”

Photo: Adobe Stock/Tyler Olson

The researchers also learned that they could reduce the solid stress within the lymph nodes using the blood pressure drug losartan. This, they believe, is a potential strategy to improve the immune response to tumors in the lymph nodes.

“Our work now leads to many important additional questions,” says Jones. “Does losartan treatment combined with immunotherapy cause the eradication of metastatic cancer cells in lymph nodes by T cell killing? And further, does this lead to a strong systemic anti-cancer immune response that helps clear the cancer from the entire body?”

The team’s findings are published in the journal Nature Biomedical Engineering. The researchers hope their work will lead to new treatment strategies for patients with metastatic cancers.

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