Structures resembling lymph nodes may lead to the destruction of cancer tumors.

It emerged after preoperative immunotherapy and may be crucial for the successful treatment of patients with hepatocellular carcinoma.

A study published in the journal Nature Immunology provides new insights into lymph node-like structures known as 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 activate the body's natural anti-cancer immunity—and their presence is associated with an enhanced treatment response. Researchers found that patients with a greater number of these structures had a lower likelihood of cancer recurrence after surgery.

However, researchers are still working to understand more deeply the role these structures play in the immune response to tumors, how they change over time, and what their presence in tumors signifies for patients.

“We have identified the life cycle of tertiary lymphoid structures in patients with liver cancer, and we conclude that these structures may be very important for the development of anti-tumor immunity and may increase the likelihood of curing cancer,” says Mark Yarchoan, an oncologist and assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.

Previously, Yarchoan and his colleagues conducted the first clinical trials of immunotherapy before surgery to remove hepatocellular carcinoma. Only a portion of patients achieved complete remission, and researchers sought to understand why.

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

Scientists found that tumors with a higher number of tertiary lymphoid structures shrank after immunotherapy and were less likely to recur after surgical removal. In contrast, tumors without these structures did not shrink and were more likely to return after surgery. A particularly favorable prognosis was observed when tertiary lymphoid structures grew in the center of the tumor rather than at its edges.

The next step for the research team will be to determine whether they can induce the formation of tertiary lymphoid structures in patients who do not develop them spontaneously after starting immunotherapy.

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

This discovery may also be relevant to other types of cancer, as the new form of tertiary lymphoid structure reported in this study has also been found by the authors in two other types of tumors known to respond to immunotherapy.