Lymph node-like structures can cause cancerous tumors to die off

Researchers at the Johns Hopkins Kimmel Cancer Center recently described the development of a lymph node-like structure in liver tumors. It occurred after preoperative immunotherapy, and may be critical to the successful treatment of patients with hepatocellular carcinoma.

The study, published in Nature Immunology, provides new information about lymph node-like structures called tertiary lymphoid structures.

These structures, which are highly organized clusters of immune B- and T-cells, are found in some patients receiving immune checkpoint inhibitors – drugs that trigger the body’s natural anti-cancer immunity – and their presence is associated with an enhanced response to treatment. The researchers found that patients who had more of these structures were less likely to have cancer recurrence after surgery.

However, researchers are still trying to further understand how these structures contribute to the immune response to tumors, how they change over time, and what their detection in tumors means for patients.

“We identified the life cycle of tertiary lymphoid structures in patients with liver cancer, and we found that these structures may be very important in generating antitumor immunity and may increase the likelihood of cancer cure,” said Mark Yarchoan, MD, an oncologist and assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.

Previously, Jarchoan and colleagues conducted the first clinical trial of immunotherapy before surgery to remove hepatocellular carcinoma. Only a subset of patients were completely cured, and the researchers were trying to understand why.

When the researchers studied these tumors, they were struck by the fact that the patients who responded to immunotherapy had tertiary lymphoid structures that had immune B cells in the center, which fight infections, and immune T cells on the outside, which destroy tumors.

Researchers found that tumors with more tertiary lymphoid structures shrank in size after immunotherapy and were less likely to relapse after surgical removal. In contrast, tumors without these structures did not shrink and were more likely to return after surgery. The prognosis was particularly favorable when tertiary lymphoid structures grew in the center of the tumor rather than along its edges.

The next step for the research team is to determine whether they can induce the formation of tertiary lymphoid structures in patients who do not develop them on their own after immunotherapy is started.

They also plan to study how different combinations of immunotherapy or other preoperative treatments affect the formation of tertiary lymphoid structures and patient outcomes.

This discovery may also have implications for other types of cancer, as the new form of tertiary lymphoid structure reported in this paper was also found by the authors in two other tumor types known to respond to immunotherapy.