Lymph Node-Like Structures Discovered Close To Brain Tumors

Researchers at Uppsala University have discovered lymph node-like structures next to the brain tumor in patients, where immune cells can be activated to attack the cancer. In a mouse model, they have also seen that immunotherapy stimulated the emergence of these structures. The discovery points to new possibilities for regulating the immune system's ability to fight tumors.

Glioma is a fatal brain tumor with a very poor prognosis. One reason it is so difficult to treat brain tumors is that the immune system, which is designed to find and destroy foreign cells, including cancer cells, has difficulty accessing the tumor due to the barriers that exist around the brain. In order for immune cells called killer T cells to fight a growing tumor, they must first be activated against the tumor in our lymph nodes, then move to the tumor and kill the cancer cells. Due to the barriers around the brain, it is difficult for the immune cells to get through.

In the research article now published in the journal Nature Communications, the researchers describe their discovery that there are lymph node-like structures in the brain as well, where killer T cells could be activated.

"It was very exciting to find lymph node-like structures in glioma patients for the first time. These structures, called tertiary lymphoid organs, are not found in the brain of healthy people and they have all the properties needed to activate immune cells in the vicinity of a tumor. This means that they could have a positive effect on the immune system's ability to fight the tumor," says Alessandra Vaccaro, a doctoral student at the Department of Immunology, Genetics and Pathology, and one of the article's first authors.

Formed near tumors

The researchers were also able to show that the appearance of tertiary lymphoid organs can be induced in mouse models with glioma. When they treated mice with immunostimulatory antibodies called αCD40, the appearance of tertiary lymphoid organs increased and they were always formed near the tumors.

"That immunotherapy can affect the emergence of tertiary lymphoid organs in the brain shows exciting opportunities to find new ways to regulate the immune system's anti-tumor response," says Anna Dimberg who has led the study.

The use of αCD40 to treat human brain tumors is currently being evaluated in several clinical trials. In the study now published, the researchers saw that αCD40 not only stimulated the formation of tertiary lymphoid organs but also, counterproductively, helped to reduce the tumor-killing ability of T cells. The study has therefore provided important knowledge about the different effects that treatment with αCD40 can give rise to.

Reference: van Hooren L, Vaccaro A, Ramachandran M, et al. Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma. Nat Commun. 2021;12(1):4127. doi: 10.1038/s41467-021-24347-7

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