Tertiary Lymphoid Structures, An Indicator of Anti-Cancer Immune Response

Tertiary lymphoid structures (TLSs) are organized collections of immune cells that resemble lymph nodes and form outside lymphoid organs, often in areas of inflammation, infection, or cancer. TLSs are thought to play an essential role in the anti-tumor immune response. They can promote immune cells’ activation and expansion, including T and B cells, in the tumor microenvironment. I would compare these with a military base, where the immune cells can hang out and get prepared to attack cancer, staying close to the tumor itself. This again supports that much of the action of the immune response is at or around the tumor, so treating directly with intratumoral immunotherapy gets you right into the heart of the action.

TLSs have been associated with improved outcomes in various cancers, including melanoma, breast and lung cancer. In addition, some studies have suggested that TLSs in the tumor microenvironment may predict response to immunotherapy.

Cancer immunotherapies that target immune checkpoints, such as PD-1/PD-L1 inhibitors, have been shown to promote the formation of TLSs in some cancer patients. In addition, some studies have suggested that other cancer treatments, especially PEF (Pulsed Electrical Field), may also promote the formation of TLSs in the tumor microenvironment.

Research is ongoing to understand better the role of TLSs in the anti-tumor immune response and to develop new strategies to target and enhance their formation in cancer patients. NanoString, which I have discussed before, can be used to identify and characterize these TLS. If successful, these strategies may provide a new approach to cancer immunotherapy that targets the formation of TLSs to promote anti-tumor immunity.